review article the formation of biofilms by pseudomonas...

Review ArticleThe Formation of Biofilms by Pseudomonas aeruginosaA Review of the Natural and Synthetic Compounds Interferingwith Control Mechanisms

Tsiry Rasamiravaka1 Quentin Labtani1 Pierre Duez2 and Mondher El Jaziri1

1 Laboratory of Plant Biotechnology Universite Libre de Bruxelles rue des Professeurs Jeener et Brachet 12 6041 Gosselies Belgium2Department of Therapeutical Chemistry and Pharmacognosy Universite de Mons Avenue Maistriau 19 Batiment Mendeleiev7000 Mons Belgium

Correspondence should be addressed to Mondher El Jaziri jaziriulbacbe

Received 29 June 2014 Revised 3 September 2014 Accepted 7 September 2014

Academic Editor Nikos Chorianopoulos

Copyright copy 2015 Tsiry Rasamiravaka et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

P aeruginosa is an opportunistic pathogenic bacterium responsible for both acute and chronic infections Beyond its naturalresistance to many drugs its ability to form biofilm a complex biological system renders ineffective the clearance by immunedefense systems and antibiotherapyThe objective of this report is to provide an overview (i) on P aeruginosa biofilm lifestyle cycle(ii) on the main key actors relevant in the regulation of biofilm formation by P aeruginosa including QS systems GacSGacA andRetSLadS two-component systems and C-di-GMP-dependent polysaccharides biosynthesis and (iii) finally on reported naturaland synthetic products that interfere with control mechanisms of biofilm formation by P aeruginosa without affecting directlybacterial viability Concluding remarks focus on perspectives to consider biofilm lifestyle as a target for eradication of resistantinfections caused by P aeruginosa

1 Introduction

The misuse and abuse of antibiotics are recognized to createselective pressure resulting in the widespread developmentof resistant bacterial strains [1 2] Antibiotics are also knownto kill ldquogoodbeneficialrdquo indigenous bacteria whichmay haveprotective role against pathogenic bacteria [3 4] Anotherimportant point to consider is that antibiotics have beenfound to be less effective in biofilm-growing bacteria [5]

Facing these limitations of antibiotics there is an increas-ing need for the discovery and the development of antimi-crobial agents that present novel or unexplored propertiesto efficiently control and manage bacterial infectious dis-eases [6] Inhibition of bacterial virulence andor biofilmformation by targeting nonmicrobicidal mechanisms areexamples of increasingly explored antipathogenic approaches[7ndash9] Among opportunistic pathogenic bacteria P aerug-inosa which produces several virulence factors is knownto be an important human and plant pathogen responsiblefor various infections particularly in immunocompromised

persons [10] Besides this the remarkable ability of P aerugi-nosa to form biofilms in many environments renders antibi-otic treatments inefficient and therefore promotes chronicinfectious diseases [5 11]

Three global nonmicrobicidal strategies have been pro-posed to struggle against pathogenic bacteria with biofilmformation ability by (i) avoiding microbial attachment to asurface (ii) disrupting biofilm development andor affectingbiofilm architecture in order to enhance the penetration ofantimicrobials and (iii) affecting biofilm maturation andorinducing its dispersion and degradation [8 12 13]

The present review covers the scope of natural com-pounds from both prokaryote and eukaryote organisms thathave been identified to disrupt biofilm lifestyle cycle inP aeruginosa without affecting directly bacterial viabilityAs a prerequisite and for a better understanding of theproposed mechanisms of action of some of the identifiedcompounds relevant key molecular actors in P aeruginosabiofilm formation and its regulation such as the chemicalsignalization machinery involved in bacteria-environment

Hindawi Publishing CorporationBioMed Research InternationalVolume 2015 Article ID 759348 17 pageshttpdxdoiorg1011552015759348

2 BioMed Research International

(b)(a)

Stage I

(c) (d) (e)

Stage II Stage III Stage IV Stage V

EPSBacteria

25120583m

8h 14h 1ndash4days 5days

1day 2days 3days 4days

2h

Figure 1 Biofilm lifestyle cycle of P aeruginosa PAO1 grown in glucose minimal media In stage I planktonic bacteria initiate attachment toan abiotic surface which becomes irreversible in stage II Stage III corresponds to microcolony formation Stage IV corresponds to biofilmmaturation and growth of the three-dimensional community Dispersion occurs in stage V and planktonic bacteria that are released fromthe biofilm to colonize other sites The biofilm formation by P aeruginosa PAO1 was revealed with Syto9 and visualized in Leica DM IRE2inverted fluorescence microscope with 400x magnification at 2 h (Stage I) 8 h (Stage II) 14 h (Stage III) 1 to 4 days (Stage IV) and 5 days(Stage V) Images represent a 250 times 250-120583m field

interaction including quorum sensing (QS) pathways will besummarized

2 Biofilm Lifestyle Cycle of P aeruginosa

Biofilm formation is an endless cycle in which organizedcommunities of bacteria are encased in a matrix of extra-cellular polymeric substances (EPS) that hold microbialcells together to a surface [14 15] these are thought to bedeterminant in 65ndash80 of all microbial infections [16ndash18] Inthis microscopic world biofilms are metaphorically called aldquocity of microbesrdquo [19 20] with EPS which represents 85 oftotal biofilm biomass as ldquohouse of the biofilm cellsrdquo [21] EPSis composed mainly of biomolecules exopolysaccharidesextracellular DNA (eDNA) and polypeptides that form

a highly hydrated polarmixture that contributes to the overallstructural scaffold and architecture of the biofilm [22ndash24]

Depending on P aeruginosa strains andor nutritionalconditions different biofilm phenotypes can be developed[25] For instance in glucose minimal media biofilm lifestylecycle of P aeruginosa PAO1 can be subdivided into fivemajor phenotypic steps (Figure 1) The process begins by thereversible adhesion of planktonic bacteria onto a surface suit-able for growth (Figure 1(a) Stage I) followed by irreversibleattachment of bacteria which thereafter form microcoloniesin EPS matrix (Figure 1(b) Stage II) Progressively bacterialmicrocolonies expand and their confluences lead to a morestructured phenotype with noncolonized space (Figure 1(c)Stage III) Then noncolonized spaces are filled with bacteriawhich finally cover the entire surface (Figure 1(d) Stage IV)

BioMed Research International 3

Meanwhile the growth of three-dimensional communities isobserved (Figure 1 Stages III and IV) Finally bacteria dis-perse from the sessile structure and reenter in planktonic stateto spread and colonize other surfaces [15 26] (Figure 1(e)Stage V)

P aeruginosa produces at least three polysaccharides(alginate Pel and Psl) that are determinant for the stabilityof the biofilm structure [27 28] Mucoid and nonmucoid Paeruginosa strains differ by the qualitative composition oftheir polysaccharides in the biofilm matrix predominantlyalginate or PslPel respectively [29ndash31] Alginate a linearunbranched polymer composed of D-mannuronic acid andL-guluronic acid [32] contributes to the structural stabilityand protection of biofilms as well as to the retention ofwater and nutrients [33] The Pel polysaccharide is mainly aglucose-rich matrix material with still unclarified composi-tion [34 35] while Psl comprises a repeating pentasaccharideconsisting of D-mannose L-rhamnose and D-glucose [36]Pel and Psl can serve as a primary structure scaffold forbiofilm development and are involved at early stages ofbiofilm formation [30 37 38]

eDNA constitutes an important functional component ofP aeruginosa biofilm matrix indeed (i) P aeruginosa biofilmformation is prevented by exposition to DNase I [39] (ii)biofilms that are deficient in eDNA have been shown to bemore sensitive to the detergent sodium dodecyl sulfate [40](iii) eDNA facilitates the twitchingmotility-mediated biofilmexpansion by maintaining coherent cell alignments [41] (iv)eDNA has been proposed to play an important role in theinitial and early development of P aeruginosa biofilms as acell-to-cell interconnecting compound [24 42 43] and (v)finally eDNAconstitutes a nutrient source for bacteria duringstarvation [44 45]

Beyond their role in bacterial motilities [46ndash48] Paeruginosa extracellular appendages flagella type IV pili andcup fimbriae are also considered to be matrix componentsthat play adhesive roles in the cell-to-surface interactions(irreversible attachment) as well as in microcolony formationin biofilms Mutants defective in flagellar-mediated motilityand mutants defective in biogenesis of the polar-localizedtype IV pili do not develop microcolonies compared to thewild type strains [49ndash51]

3 Overview of Global RegulatingSystems Involved in P aeruginosaBiofilm Formation

The complex regulation of biofilm formation involves multi-ple bacterial machineries including the QS systems and thetwo-component regulatory systems that both interact mainlywith EPS production [52] Deficiency in the network regula-tion required for biofilm matrix formation effectively resultsin the alteration of the biofilm structure and architecture andtherefore of its protective role The main key actors relevantin the regulation of biofilm formation by P aeruginosa aresummarized in Figure 2

31 QS Mechanisms and Biofilm Formation QS is a cell-to-cell communication used by many bacteria to detect theirpopulation density by producing and perceiving diffusiblesignal molecules that coordinate virulence factors produc-tion motility and biofilm formation [53 54] P aeruginosapossesses two main QS systems (las and rhl) which drivethe production (throughout synthases LasI and RhlI) and theperception (by the transcription factors LasR and RhlR) ofthe autoinducer signaling molecules N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL) and N-butanoyl-L-homoserine lactone (C4-HSL) (Figure 3(a)) respectively[54] A third QS system based on quinolone signals (PQSsystem) interacts with the acyl homoserine lactones (AHLs)systems in an intricate way [54]

Davies et al [55] have evidenced the role of the las systemfor biofilm formation and maturation compared to wildtype biofilm the biofilm of lasI mutant appears flat undif-ferentiated and quickly dispersed from the surface uponexposure to sodium dodecyl sulfate The precise implicationof las system in biofilm formation is not yet clear HoweverGilbert et al [56] reported that the QS regulator LasR canbind to the promoter region of the psl operon suggestingthat QS can regulate psl expression The rhl system has beenreported to intervene in P aeruginosa biofilm formation [57]by enhancing Pel polysaccharide biosynthesis transcriptionof the pel operon is actually reduced in rhlI mutant The PQSsystem for its part is linked to eDNA release during biofilmdevelopment biofilm formed by pqsA mutant contains lesseDNA than biofilm formed by the wild type [40 42] Alltogether these data indicate that the three QS systems knownin P aeruginosa play roles in biofilm lifestyle cycle

Importantly an indirect link between biofilm formationand QS has been reported through the control of swarmingand twitching motilities as well as rhamnolipids and lectinsproduction The swarming motility a form of organizedsurface translocation depends on extensive flagellation andcell-to-cell contact [58 59] regulated by the rhl system[60] swarming motility is implicated in early stages ofP aeruginosa biofilm establishment Strains grown underconditions that promote swarming motility (growth mediumwith glutamate or succinate as carbon source) form flat anduniform biofilmwhile strains with limited swarmingmotilityresult in biofilm containing nonconfluent cell aggregates [25]Twitching motility a flagella-independent form of bacterialtranslocation occurs by successive extension and retractionof polar type IV pili [47] Known to be regulated by therhl system on Fe-limited minimal medium [61] twitchingmotilities are necessary for the assembly of a monolayer ofP aeruginosa cells into microcolonies [49]

Beyond their biosurfactant and virulence factor roles[62] rhamnolipids whose production is under the rhl systemcontrol [63] present multiple roles in biofilm formation byP aeruginosa Indeed they are believed to be involved in (i)forming microcolonies [64] (ii) maintaining open channelstructures that prevent bacterial colonization by disruptingboth cell-to-cell and cell-to-surface interactions [26] (iii)facilitating three-dimensional mushroom-shaped structuresformation in P aeruginosa biofilms [64] and (iv) facilitat-ing the cell dispersion from the biofilm as P aeruginosa


pslA-L pelA-G algA-44-X

c-di-GMP

Rhamnolipids Lectins (LecA LecB)

Swarming Twitching

Psl Pel AlginateeDNA

Components and mechanisms involved in biofilm formation

1

2

3

GacSRetS LadSP

Input signal(s)

GacAP

RsmA

RsmZY

+ rsmA

GacA

RR

RR

las system rhl systemlasR lasI rhlR rhlI

LasR3-oxo-C12-HSL

RhlRC4-HSL

RhlILasI

PQS system

Figure 2 Relevant bacterial systems and factors implicated in the regulation of P aeruginosa biofilm formation (1) Quorum sensing system(2) Two-component regulatory system GacSGacA and RetSLadS (RR response regulator domain receiver P phosphorylation) pathway(3) Exopolysaccharides production and c-di-GMP pool regulation See text for explanation

variants which produce more rhamnolipids than wild-typeP aeruginosa exhibit hyper-detaching properties [65 66]Finally the cytotoxic virulence factor galactophilic lectinsLecA and LecB has been proposed to contribute to biofilmdevelopment in P aeruginosa since LecA and LecB mutantsform thin biofilms as compared to the wild type bacteria[67 68] Both LecA and LecB expressions are regulated bythe rhl QS system [69]

32 Biofilm Regulation by GacSGacA and RetSLadS Two-Component Systems Among the 60 two-components sys-tems found in the genome of P aeruginosa [70] theGacSGacA system acts as a super-regulator of the QS systemand is involved in the production of multiple virulencefactors as well as in biofilm formation [71] The Gac systemconsists of a transmembrane sensor kinase (GacS) thatupon autophosphorylation transfers a phosphate group to

its cognate regulator (GacA) which in turn upregulates theexpression of the small regulatory RNAs (RsmZ and RsmY)RsmZ and RsmY capture the small RNA-binding regulatoryprotein RsmA (encoded by rsmA gene) a repressor thatposttranscriptionally regulates the psl locus (pslA-L) [72ndash74]The GacSGacA system also has a control on the AHL systemas it inactivates free RsmA which negatively controls thesynthesis of C4-HSL and 3-oxo-C12-HSL and therefore theextracellular virulence factors controlled by the las and rhlsystems [75ndash77]

The hybrid sensor histidine kinase RetS is known torepress biofilm formation [78 79] whereas the histidinekinase LadS antagonizes the effect of RetS [80] Indeed ΔretSmutant form more structured biofilms as compared to wildtype P aeruginosa PAO1 [78] the PA14 strain (naturallydeficient in ladS gene) displays attenuated biofilm formationcompared to PA14 LadS+ strain [81] It is reported that RetS


ON

HO

O

ON

HO

O O

C4-HSL

3-Oxo-C12-HSL

(a) Native AHLs

3-Oxo-C12-cyclohexanone

N-(4-bromo-phenylacetanoyl)-L-HSL

N-Acylcyclopentylamines

N-(indole-3-butanoyl)-L-HSL

NH

N

N

H

H H

O

O

NH

OnO

O

OO

NH H O

OO

Br

C9H19

(b) AHLs analogues

X = H furanone C-56X = Br furanone C-30

Penicillic acidPatulin

Manoalide

O

O O

OO

O

O

XH

OOH

OH

Br

OO

O

OH

HO

(c) Compounds with lactone ring analogues

Figure 3 Structure of natural and synthetic AHL-based compounds which inhibit biofilm formation by P aeruginosa (a) Native N-acyl-l-homoserine lactone signal molecules of P aeruginosa (C4-HSL and 3-oxo-C12-HSL) (b) synthetic analogue of AHLs with side aromatics andsynthetic analogues of AHLs with modified lactone rings and (c) natural (manoalide penicillic acid and patulin) and synthetic (furanones)compounds with lactone ring analogues

and LadS interact with the GacSGacA system by modulat-ing the phosphorylation state of GacS which consequentlyinhibits and promotes respectively the phosphorylation ofGacA [82 83]

It is interesting to note that GacSGacA and RetSLadSsystems are proposed to be involved in mediating the transi-tion of the P aeruginosa phenotype from an acute to chronicphase infection [78]

33 C-di-GMP-Dependent Polysaccharides Biosynthesis andBiofilm Formation Polysaccharides production is dependenton the intracellular pool of bis-(31015840-51015840)-cyclic dimeric guano-sinemonophosphate (c-di-GMP) [84 85] a ubiquitous intra-cellular secondmessenger widely distributed in bacteria [86]In bacterial cells c-di-GMP is generated from two moleculesof guanosine triphosphate by diguanylate cyclases and brokendown into 2-GMP by specific phosphodiesterases [86]


High levels of c-di-GMP promote the biosynthesis ofpolysaccharides (alginate and Pel) Indeed a binding processof c-di-GMP to PelD and Alg44 proteins is required forPel and alginate polymer formation respectively [85 87]However the exact molecular mechanism by which thisinteraction regulates the polymerization of sugar precursorsis not known

Conversely low levels of c-di-GMP promote bacterialmotilities by enhancing flagellar formation and bacterialdispersion [85]

4 Natural and Synthetic Products That AffectP aeruginosa Biofilm Formation

Plants and animals are naturally exposed to bacterial infec-tions and they respond to bacterial components and signalmolecules in different manners including the activation ofdefense mechanisms andor the expression of stress manage-ment genes [88ndash93] Therefore it is obvious to expect thateukaryotes have developed chemical mechanisms to combatpathogens by killing them or silencing virulencemechanismssuch as QS system andor biofilm formation Tables 1 and 2summarize the reported natural and synthetic products thataffect P aeruginosa biofilm formation

41 Antibiofilm Compounds with Anti-QS Activity Severalclasses of molecules have been reported to present bothantibiofilm formation and anti-QS properties in P aeruginosa[94ndash96]

Some AHL analogues (Figure 3(b)) have been shown toexhibit this double inhibitory activity Geske et al [97] havereported that synthetic analogues of AHLs with additionalaromatic moieties [N-(indole-3-butanoyl)-L-HSL and N-(4-bromo-phenylacetanoyl)-L-HSL] display inhibitory activityon LasR-based QS system as well as biofilm formation inP aeruginosa PAO1 Synthetic AHLs analogues where thehomoserine lactone ring is replaced by a cyclohexanone ringdownregulate expression of the LasI AHL synthase resultingin a reduced expression of the virulence factors pyocyaninand elastase and in an alteration of biofilmmorphologyphe-notype [98]Nonhydrolysable cyclopentyl analogues ofAHLs(N-acyle cyclopentylamides) inhibit the lasI and rhlA expres-sion the production of virulence factors including elastasepyocyanin and rhamnolipids and the biofilm formationwithout affecting bacterial growth [99]

Halogenated furanones (particularly furanones C-30 andC-56) inspired from natural compounds produced by themarine macroalga Delisea pulchra exhibit biofilm reductionand target the las and rhl systems in P aeruginosa [55 100101] Besides inmouse lungs infected with P aeruginosa theywere found to inhibit bacterial colonization to improve theclearance of bacteria from the host and to reduce the tissuedamage [102]

Among the macrolide antibiotics azithromycin derivedfrom Saccharopolyspora erythraea has been the most investi-gated anti-QS antibiotic that presents a strongQS and biofilminhibitory effect in P aeruginosa [103ndash105] Indeed at subin-hibitory azithromycin concentration (2120583gmL)P aeruginosa

produces lower AHL signal molecules and virulence factors[106 107] suggesting that the observed biofilm inhibition isat least partially due to the reduction of both C4-HSL and3-oxo-C12-HSL production [108] Interestingly azithromycinhas been reported to diminish the expression of GacA butalso RsmA at translational level [109] to inhibit the synthesisof alginate [103] and to reduce the three types of motility(swimming swarming and twitching) [110]

Penicillic acid and patulin two secondary fungalmetabo-lites from Penicillium species were shown to effect QS-controlled gene expression in P aeruginosa most likely byaffecting the RhlR and LasR regulatory proteins at posttran-scriptional level In vitro studies showed that P aeruginosaPAO1 biofilms treated with patulin and tobramycin wereconsiderably more susceptible to the antibiotic as comparedto control biofilms exposed to either tobramycin or patulinalone [111] However treatment with patulin alone did notaffect development of the biofilm and no hypothesis of mech-anisms of action was proposed by authors The genotoxicityof patulin certainly limits its potential usefulness [112]

Manoalide a sesterterpenoid from the marine organismLuffariella variabilis exhibits antibiofilm and anti-QS activi-ties (las system) in P aeruginosa without bactericidal effects[113] although presenting antibiotic activity against gram-positive bacteria [114]

Solenopsin A alkaloid isolated from the ant Solenopsisinvicta inhibits P aeruginosa pyocyanin production proba-bly throughdisruption of the rhl signaling systemand reducesbiofilm production in a dose-dependent manner [115]

Mammalian cells release enzymes called paraoxonases 1(extracted from human and murine sera) that have lactonaseactivity degrading P aeruginosa AHLs they prevent in anindirect way QS and biofilm formation [116 117]

Thephenolic compound curcumin amajor constituent ofturmeric roots (Curcuma longa L) downregulates virulencefactors (pyocyanin elastase and protease) in P aeruginosaPAO1 and inhibits adherence of the bacteria to polypropylenesurfaces This was correlated with a decrease in 3-oxo-C12-HSL production [118] Rosmarinic acid a natural phenoliccompound produced by the root of Ocimum basilicum Lupon P aeruginosa infection prevents biofilm formation butfails to penetrate mature biofilm under in vivo and in vitroconditions [89] Structure-based virtual screenings againstLasR and RhlR receptor proteins effectively indicate thatrosmarinic acid is a potential QS inhibitor [119] Ellagic acidderivatives from Terminalia chebula Retz have been shownto downregulate lasIR and rhlIR genes expression with aconcomitant AHLs decrease resulting in the attenuation ofvirulence factor production and in an enhanced sensitivityof biofilm towards tobramycin [120] Girennavar et al [121]demonstrated that the furocoumarins from grapefruit juicebergamottin and dihydroxybergamottin inhibit the activitiesof the autoinducers AI-1 (N-3 hydroxybutanoyl-homoserinelactone) and AI-2 (furanosyl borate diester) in a V harveyibioassay Besides these authors showed that AI-1 and AI-2 inhibit biofilm formation in E coli O157H7 Salmonellatyphimurium and P aeruginosa without affecting bacterialgrowth However the mechanisms of action remain unclear


Table1Naturalinhibitory

compo

unds

forP

aeruginosabiofi

lmform

ation

Naturalprod

uctscompo

unds

Orig

inClass

Activ

ities

References

QSinhibitio

nBiofi

lminhibitio

n(a)

Disp

ersio

nprom

otion

Synergywith

antib

iotic

Alginatelyase

Paeruginosa

Enzyme

minus+

++(1)

[134]

Ursolicacid

Diospyros

dend

oWelw

Triterpenoid

minus+(24h

)motility

NC

NC

[141]

p-Cou

maroyl-h

ydroxy-ursolicacid

Diospyros

dend

oWelw

Cou

maratee

stero

ftriterpene

NC

+(24h

)NC

NC

[142]

Zingeron

eZingiberoffi

cinaleR

osc

Phenoliccompo

und

NC

+(168

h)c-di-G

MP

NC

+(2)

[138139]

Casbaned

iterpene

Croton

nepetaefo

liusB

aill

Diterpenoid

NC

+(24h

)adherence

NC

NC

[140]

DNaseI

Bovine

pancreas

Enzyme

NC

+(18ndash24

h)+

+(3)

[137]

DNase-1L2

Hum

anstratum

corneum

[136]

Paraoxon

ases

1Hum

anandmurines

era

Enzyme(lacton

ase)

++(24h

)NC

NC

[116117]

Manoalid

eLu

ffarie

llavaria

bilis

(Polejaeff

1884)

(marineo

rganism

)Seste

rterpeno

id+(la

ssystem)

+(24h

)NC

NC

[113114]

Soleno

psin

ASolen

opsis

invicta(in

sectant)

Alkaloid

+(rhlsyste

m)

+(24h

)NC

NC

[115]

Catechin

Combretum

albiflorum

(Tul)Jong

kind

Flavon

oid

+(la

srhlsyste

ms)

+(24h

)NC

NC

[124]

Naringenin

Com

mercial

Flavon

oid

+(la

srhlsyste

ms)

+(48h

)NC

NC

[125]

Cou

maratee

ster

Dtrichocarpa

Baker

Phenoliccompo

und

+(la

srhlsyste

ms)

+(48h

)+

+(1)

[126]

Ajoene

Alliu

msativ

umL

Organosulfur

+(la

srhlsyste

ms)

+(96h

)NC

+(1)

[130]

Ellagica

cidderiv

atives

Term

inaliachebulaRe

tz

Phenoliccompo

und

+(la

srhlsyste

ms)

+(72h

)NC

+(1)

[120]

Rosm

arinicacid

Ocim

umbasilicu

mL

Phenoliccompo

und

+(la

srhlsyste

ms)

+(18h

)minus

NC

[89119

]

Eugeno

lSyzygium

arom

aticu

m(L)

MerrEt

Perry

Phenylprop

anoid

+(la

spqs

syste

ms)

+(24h

)NC

NC

[128]

Curcum

inCu

rcum

alongaL

Phenoliccompo

und

+(A

HLs)

+(48h

)NC

NC

[118]

Bergam

ottin

and

dihydroxybergamottin

Citru

sparadisi

Macfad

(Rio

RedandMarsh

Whitegrapefruits)

Furocoum

arins

+(A

I-1and

AI-2)

+(24h

)NC

NC

[121]

Penicillica

cid

Penicilliu

mspecies

Furano

ne+(LasR

RhlR)

NC

NC

NC

[111]

Patulin

Furopyrano

ne+(LasRRh

lR)

mdashDagger

NC

+(1)

Emod

inRh

eum

palm

atum

LAnthraquino

ne+(docking

traR

)+(72h

)NC

+(3)

[123]

Baicalein

Scutellariabaica

lensis

Georgi

Flavon

oid

+(docking

traR

)+(72h

)NC

+(3)

[122]

+yesminusnoNC

notcom

mun

icated

DaggerPatulin

does

notaffectthed

evelo

pmento

fbiofilm

(a) Exp

erim

entd

uration

(1) A

minoglycosid

es(2)ciprofl

oxacin(3)am

picillin


Table2Synthetic

inhibitory

compo

unds

inPaeruginosa

biofi

lmform

ation

Synthetic

compo

unds

(Naturalcompo

undorigin)

Activ

ities

References

QSinhibitio

nBiofi

lminhibitio

n(a)

Disp

ersio

nprom

otion

Synergisticantib

iotic

andor

immun

edefense

effect

TAGEandCA

GE(Bromoageliferin)

NC

+(24h

)+

NC

[132]

Dihydrosventrin

(Sventrin

)NC

+(24h

)+

NC

[133]

N-(4-brom

o-ph

enylacetanoyl)-l-H

SL

N-(indo

le-3-butanoyl)-L-HSL

(AHLs)

+AHLs

antagonist(la

ssystem)

+(24h

)NC

NC

[97]

3-oxo-C1

2-cyclo

hexano

ne(A

HLs)

+AHLs

antagonist(la

ssystem)

+(24h

)NC

NC

[98]

C10-cyclo

pentylam

ide(AHLs)

+(la

sIandrhlA)

+(24h

)NC

NC

[99]

Furano

neC-

30andC-

56(Furanon

e)+(la

srhlsystems)

+(24h

)[55100101]

S-ph

enyl-L-cysteinesulfoxide

(Cysteinesulfoxide

alliin)

+(la

srhlsystems)

+(24h

)NC

NC

[148]

Diphenyld

isulfide

(Disu

lfide

deriv

atives

ofthea

lliinase

mediatedreactio

ns)

+lassystem

+(24h

)NC

NC

AzythromycinDagger

(Erythromycin)

+(gacA

lasa

ndrhlsystems)

+(72h

)+

+(1)

[103108109]

+yesminusnoNC

notcom

mun

icated

DaggerAt

subinh

ibito

ryconcentration

(a) Exp

erim

entd

uration

(1) A

minoglycosid

es


Curcumin Catechin

Bergamottin

Zingerone

Rosmarinic acid

Ellagic acid derivative

Naringenin

Baicalein

Eugenol

Dihydroxybergamottin

HO

HO

HO

OHOH

OH

OHOH

OH

OH

OH

OH

OHO

OO

O

OO

O OHOH

OHOH

O

OR

O

HO

HOHO

HO

HO

HOHO

OH

OH

OH

O

O

O

O

Coumarate esterDagger

O O O

O

O O

O

O

O O

O

OCH3

OCH3

OCH3 H3CO

DaggerRadical under elucidation

Figure 4 Phenolic compounds and derivatives with antibiofilm and anti-QS proprieties

Docking screening for QS inhibitors predicted that theflavone baicalein obtained from the roots of Scutellariabaicalensis Georgi could interact with A tumefaciens QStranscription activator protein TraR Effectively at 20120583Mbaicalein promotes the proteolysis of the signal receptor TraRprotein in Escherichia coli biosensor significantly inhibitingthe biofilm formation by P aeruginosa [122] Similarly thescreening of traditional Chinese medicinal plants identifiedthe anthraquinone emodin extracted from rhubarb (Rheumpalmatum L) emodin actually inhibits the P aeruginosabiofilm formation at 20120583M increasing the activity of ampi-cillin [123]

The flavan-3-ol catechin isolated from the bark of Com-bretum albiflorum (Tul) Jongkind as well as the flavanonenaringenin both at 4mM final concentration do interferewith QS mechanism in P aeruginosa PAO1 by affectingautoinducers perception and biofilm formation [124ndash126] Acoumarate ester isolated from the bark extract of MalagasyendemicDalbergia trichocarpa Baker interferes with P aerug-inosaQS systems (las and rhl) inhibits the biofilm formationand increases the effectiveness of the antibiotic tobramycinin killing biofilm-encapsulated P aeruginosa [126] (Figures 4and 5)

Recently Meliaceae Melastomataceae Lepidobotryaceaeand Sapindaceae collected from neotropical rainforests inCosta Rica presented significant anti-QS activities in a Chro-mobacterium violaceum bioassay andor inhibition of biofilmformation by P aeruginosa PA14 [127] Although the exact

natures of the active constituents are not yet elucidated theauthors suggest that they could belong to polar polyphenolssimilar to tannic acid

A recent screening of various herbal extracts revealedthat clove extract (Syzygium aromaticum (L) Merr Et Perry)inhibits QS-controlled gene expression (las and pqs systems)in P aeruginosa with eugenol as major active constituent[128] Eugenol at subinhibitory concentrations (400 120583M)inhibited virulence factors production including elastasepyocyanin and biofilm formation In agreement with thisfinding subinhibitory concentrations of the clove essential oilsignificantly reduces las- and rhl-regulated virulence factorsexopolysaccharide production and biofilm formation by Paeruginosa PAO1 [129]

Ajoene an allyl sulfide isolated from garlic (Alliumsativum L) has been reported to affect QS-regulated genesin P aeruginosa including the production of rhamno-lipids Additionally ajoene synergizes with the antibiotictobramycin in killing biofilm-encapsulated P aeruginosaimproving the clearance of P aeruginosa from lungs in amouse model of pulmonary infection [130] A naturally-inspired organosulfur compound (S-phenyl-L-cysteine sul-foxide) and its derivative (diphenyl disulfide) have beenreported to significantly reduce the amount of biofilm forma-tion by P aeruginosa [131] The S-phenyl-L-cysteine sulfoxideantagonizes both the las and rhl QS systems whereas thediphenyl disulfide only interferes with the las system


Two-day old culture

Two-day old cultureOne-day old culture +CE at culture initiation

One-day old culture +DMSO at culture initiation

(a) (b)

+ tobramycin (100120583gmL)


Figure 5 P aeruginosa biofilm phenotypes and effectiveness of tobramycin treatment in presence of DMSO 1 or coumarate ester (CE) at300 120583gmL (a) After 1 day of incubation P aeruginosa fails to form structured confluent aggregate in presence of CE as compared to DMSOtreatment (b) CE considerably increases the susceptibility of P aeruginosa to tobramycin (100 120583gmL) as shown by the increased proportionof dead cells compared with DMSO The bacterial viability was assessed by staining the cells with SYTO-9 (green areasmdashlive bacteria) andpropidium iodide (red areasmdashdead bacteria) furnished in the LIVEDEADBacLight kit Cells were visualized using a LeicaDM IRE2 invertedfluorescence microscope using a 40x objective lens and colored images were assembled using Adobe Photoshop

42 Antibiofilm Compounds without or with Unspecified Anti-QS Activity Various organisms including prokaryotes andeukaryotes (marine organisms animals and plants) havebeen reported to produce secondary metabolites which exertantibiofilm activity Some of those natural compounds havebeen used as models to build synthetic antibiofilm com-pounds against P aeruginosa

Bromoageliferin pyrrole-imidazole alkaloids frommarine sponges (Agelas conifer Agelaceae) has been thescaffolding for the development of two derivatives trans-bromoageliferin analogue 1 (TAGE) and cis-bromoageliferinanalogue 2 (CAGE) Both synthetic derivatives inhibit biofilmformation and furthermore are able to disperse preexistingP aeruginosa PAO1 biofilms without demonstrating abactericidal or growth-inhibiting effect [132] Analoguesbased upon the oroidin template parent molecules of bro-moageliferin have been synthesized and screened in P aeru-ginosa for their antibiofilm ability [133] The authors foundthat the most potent analogue turned out to be dihydro-sventrin a variant of the pyrrole-imidazole alkaloids sventrin(from Agelas sventres) which exhibits biofilm inhibition andbiofilm dispersion for different strains of P aeruginosawithout any microbicidal activity

Alginate lyase produced by P aeruginosa itself promotesbiofilm dispersion and acts synergically with antibiotics forsuccessful elimination of mucoid strains of P aeruginosaestablished in the respiratory tracts of cystic fibrosis patients[134] However a recent study demonstrated that this effect

cannot be attributed to the catalytic activity of the enzymeIndeed bovine serum albumin or simple amino acids leadto the same results The authors postulate that alginatelyase acts simply as a nutrient source modulating cellularmetabolism and thus inducing cellular detachment andenhancing tobramycin efficacy [135]

Bovine pancreatic Dnase I andDnase-1L2 extracted fromhuman stratum corneum exhibited strong antibiofilm activityinP aeruginosa [136] Indeed the degradation of extracellularDNA leads to an altered biofilm that permits increasedantibiotics penetration [137]

Extracts of Ginger (Zingiber officinale Rosc) long usedby Indians Asians and Arabs to treat numerous ailments[137] inhibit P aeruginosa PA14 biofilm formation throughthe reduction of c-di-GMP production and consequentreduction of total polysaccharides production [138] Theginger extract revealed no AHL-based QS inhibition inthe Chromobacterium violaceum CV026 and Agrobacteriumtumefaciens NT1 reporter biosensor systems The majorcomponent of dry ginger root zingerone (vanillyl acetone)has been shown to inhibit biofilm formation to increase thesusceptibility of P aeruginosa PAO1 to ciprofloxacin [139]and to inhibit swimming swarming and twitchingmotilitiesHowever authors did not propose any mechanism of action

The casbane diterpene isolated from the ethanolic extractofCroton nepetaefoliusBaill a plant native fromnortheasternBrazil inhibits biofilm formation in several clinical relevantspecies including P aeruginosa (at 250120583gmL) without


affecting the planktonic growth Authors suggest that thisinhibition of biofilm formation may be related to an inter-action between casbane diterpene and lipopolysaccharidespresent on the cell surface whichmight affect their adherenceproperties [140]

Ursolic acid (3120573-hydroxy-urs-12-en-28-oic acid) fromDiospyros dendo Welw is identified to inhibit biofilm for-mation without interfering with QS systems in E coli Paeruginosa andV harveyi ursolic acid at 10 120583gmL has beenfound to reduce 72 of E coli JM109 biofilm Transcriptomicanalyses led to the conclusion that ursolic acid inhibitsbiofilm formation by inducingmotility [141]The 3120573-O-cis-p-coumaroyl-20120573-hydroxy-12-ursen-28-oic acid isolated fromthe same plant strongly inhibits biofilm formation by Paeruginosa PAO1 [142] However the mechanism of activitywas not investigated

5 Concluding Remarks and Perspectives

There is increasing evidence that biofilm-mediated infectionfacilitates the development of chronic infectious diseases andrecurrent infections [143ndash145] Relevance in using antibiofilmcompounds is based on the restoration of antibiotic effective-ness by facilitating their penetration through compromisedbiofilm structure Moreover a degradation of the biofilmmatrix could render infectious bacteria reachable to immunedefenses (eg polymorphonuclear leukocytes innate andspecific antibodies) [146 147] Thus antibiofilm compoundscould be interesting antibiotic adjuvants to prevent or treatchronic infections Similarly relevance in using anti-QScompounds is based on the concomitant drastic reductionof virulence factors expression which gives the necessarytime for immune defense systems to elaborate appropriateresponses by the recruitment of immune cells and productionof specific antibodies Unlike antibiofilm compounds anti-QS compounds are interesting to prevent or jugulate acuteinfection However it should also be noted that (i) anti-QSand antibiofilm compoundsmay lose their appeal in immunecompromised patients who often harbor bacteria that arestill alive but present in a disorganized and less virulentstage (ii) QS systems do not control the totality of virulencefactors expression and (iii) the development of anti-QSbacterial resistance cannot be excluded [148] These factspartly explainwhy the discovery ofQSmodulators has not yetled to major therapeutic breakthroughs In our opinion suchbioactive compounds will probably not substitute antibioticsbut rather optimize the effectiveness of infectious diseasestreatment notably through biofilm disruption and antibioticdose reduction their use is also appealing to optimize the useof microbicidal products by reducing biofilm encroachmenton biomaterials and medical devices

In the perspective of therapeutic application very fewstudies have been progressed to clinical trial To the best ofour knowledge garlic is the only extract with anti-QS andantibiofilm to have been tested in a clinical trial with non-significant results contrary to its drastic in vitro bioactivityeffect [149] One reason of this fact is that behavior of clinicalisolates may be different when grown in laboratory condition

and in human body which could lead to unexpected biofilmdevelopment Thus before progressing in clinical trial ofrelevant bioactive compounds effort on the improvementof experimental in vitro and in vivo conditions should beaddressed and clinical trial protocols should be discussed

Potent antibiofilm agents are considered interesting ifthey exert a sustainable bioactivity this can be indicated by anactivity that resists accumulating bacterial toxins enzymesand metabolites for more than 48 h in culture media Asless than half of bioactive products have been tested upto 48 hours further investigations are warranted to selectthose compoundswith sustained activities whichwould havemore chances to be active in clinical conditions Halogenatedfuranones have been widely studied for their powerful anti-QS and antibiofilm activities (lt10 120583M) [100] However theirtoxic and carcinogenic properties relegate them so far tothe role of positive QS inhibitory controls in laboratoryexperiments [150 151] In this regard herbal phenolic com-pounds and their derivatives frequent in food componentsand more particularly those already present in popularand approved herbal drugs (ie rosmarinic acid in Melissaofficinalis L) are promising candidates to develop antibiofilmagents however structure-activity studies are still requiredto better assign essential structural features responsible forantibiofilm activity In the same perspective searching forcompounds active at nanomolar levels should be privileged asthese could presumably present lower toxicity risks The QSsystem is an obvious target for biofilm-associated infectionsas QS interacts directly andor indirectly in different stepsof biofilm formation Intriguingly even if QS inhibitionis the most extensively studied approach against P aerug-inosa several anti-QS natural compounds have not beenyet investigated for their antibiofilm activity (eg humansexual hormones and some antibiotics at subinhibitory con-centration notably ceftazidime and ciprofloxacin) [103 152]Attractive therapeutic agents are those which modulate QSsystem(s) with an extending or particular impact on biofilmlifestyle they could then be helpful as a preventive or curativeapproach and at every step of infectious diseases (acute andchronic) However finding universal antibiofilm compoundsrepresents a challenge as biofilm lifestyle composition andphenotype strongly depend on several parameters such asnutritional conditions In this regard we support the hypoth-esis that compounds which target GacSGacA pathway areworthy of interest with respect to the pathway hierarchicallyupstream position that controls positively both QS systemand exopolysaccharides biosynthesis (Psl) (Figure 2) Suchcompounds could possibly impair almost all the biofilmlifestyle cycle of P aeruginosa from irreversible attachmentto dispersion stages (Table 3) and could be powerful alliesfor conventional antibiotics in the struggle against bacterialbiofilm-mediated infections [8 12 95]

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper


Table3Factorsa

ffectingbiofi

lmlifestyleregu

latio

n

Biofi

lmlifestylecycle

StageI

Reversibleattachment

StageII

Irreversibleattachment

StageIII

Maturation-1

(microcolony

developm

ent)

StageIV

Maturation-2

(maintenance)

StageV

Disp

ersio

n

Implicated

factors

c-di-G

MP

(i)Flagellaa

ndtype

IVpili

(ii)A

dhesins

(iii)PslPel

(i)Cell-to-cellcommun

ication

lasI

(ii)T

ypeIVfim

briae

(iii)Matrix

compo

nentsPsl

PeleD

NA

(iv)L

ectin

AB

(v)rhlA


ication

(ii)M

atrix

compo

nentsPslPel

eDNA

(iii)rhlA

Rham

nolip

ids

Generaltarget

(i)Prom

otingplankton

iclifestyle

(ii)B

lockingsw

itchfro

mplankton

icto

biofi

lmlifestyle

Redu

cing

initialadhesio

nandinteraction

Interfe

ringwith

QS

commun

ication

(i)Re

activ

atingmetabolic

activ

ityfora

ntibiotic

efficiency

(ii)Interferin

gwith

QS

commun

ication

Prom

otingdispersio

nand

degradation

Exam

ples

ofextractsor

compo

unds

(i)Gingere

xtract

(ii)U

rsolicacid

(i)Ca

sbaned

iterpene

(ii)C

oumaratee

ster

Cou

maratee

ster

(i)Soleno

psin

A(ii)N

aringenin

(iii)Fu

rano

neC-

30and-56

(iv)F

lavan-3-olC

atechin

(v)A

joene

(vi)Cou

maratee

ster

DNAs

eI1L2


Acknowledgment

Theauthorswould like to thankCUD (CommissionUniver-sitaire pour leDeveloppement Belgium) for financial supportthroughout the project PIC-Madagascar 2009

References

[1] L C Epps andPDWalker ldquoFluoroquinolone consumption andemerging resistancerdquoUSPharmacology vol 10 pp 47ndash54 2006

[2] B K English and A H Gaur ldquoThe use and abuse of antibioticsand the development of antibiotic resistancerdquo Advances inExperimental Medicine and Biology vol 659 pp 73ndash82 2010

[3] F Guarner and J-R Malagelada ldquoGut flora in health anddiseaserdquoThe Lancet vol 361 no 9356 pp 512ndash519 2003

[4] L Beaugerie and J-C Petit ldquoAntibiotic-associated diarrhoeardquoBest Practice amp Research Clinical Gastroenterology vol 18 no2 pp 337ndash352 2004

[5] NHoslashiby O Ciofu andT Bjarnsholt ldquoPseudomonas aeruginosabiofilms in cystic fibrosisrdquo FutureMicrobiology vol 5 no 11 pp1663ndash1674 2010

[6] L Cegelski G R Marshall G R Eldridge and S J HultgrenldquoThe biology and future prospects of antivirulence therapiesrdquoNature Reviews Microbiology vol 6 no 1 pp 17ndash27 2008

[7] V C Kalia and H J Purohit ldquoQuenching the quorum sensingsystem potential antibacterial drug targetsrdquo Critical Reviews inMicrobiology vol 37 no 2 pp 121ndash140 2011

[8] M S Blackledge R J Worthington and C Melander ldquoBiologi-cally inspired strategies for combating bacterial biofilmsrdquo Cur-rent Opinion in Pharmacology vol 13 no 5 pp 699ndash706 2013

[9] G Sharma S Rao A Bansal S Dang S Gupta and R GabranildquoPseudomonas aeruginosa biofilm potential therapeutic tar-getsrdquo Biologicals vol 42 no 1 pp 1ndash7 2014

[10] A Deep U Chaudhary and V Gupta ldquoQuorum sensing andbacterial pathogenicity from molecules to diseaserdquo Journal ofLaboratory Physicians vol 3 no 1 pp 4ndash11 2011

[11] T Bjarnsholt ldquoThe role of bacterial biofilms in chronic infec-tionsrdquo APMIS Supplementum no 136 pp 1ndash51 2013

[12] L Yang Y LiuHWu et al ldquoCombating biofilmsrdquoFEMS Immu-nology amp Medical Microbiology vol 65 no 2 pp 146ndash157 2012

[13] J Masak A Cejkova O Schreiberova and T Rezanka ldquoPseu-domonas biofilms possibilities of their controlrdquo FEMSMicrobi-ology and Ecology vol 89 no 1 pp 1ndash14 2014

[14] R M Donlan ldquoBiofilms microbial life on surfacesrdquo EmergingInfectious Diseases vol 8 no 9 pp 881ndash890 2002

[15] E Karatan and P Watnick ldquoSignals regulatory networks andmaterials that build and break bacterial biofilmsrdquoMicrobiologyand Molecular Biology Reviews vol 73 no 2 pp 310ndash347 2009

[16] J W Costerton P S Stewart and E P Greenberg ldquoBacterialbiofilms a common cause of persistent infectionsrdquo Science vol284 no 5418 pp 1318ndash1322 1999

[17] M Chicurel ldquoBacterial biofilms and infections SlimebustersrdquoNature vol 408 no 6810 pp 284ndash286 2000

[18] M Hentzer L Eberl and M Givskov ldquoTranscriptome analysisof Pseudomonas aeruginosa biofilm development anaerobicrespiration and iron limitationrdquo Biofilms vol 2 no 1 pp 37ndash61 2005

[19] P Watnick and R Kolter ldquoBiofilm city of microbesrdquo Journal ofBacteriology vol 182 no 10 pp 2675ndash2679 2000

[20] I A Nikolaev and V K Plakunov ldquoBiofilm ldquoCity of microbesrdquoor an analogue of multicellular organismsrdquoMikrobiologiia vol76 no 2 pp 149ndash163 2007

[21] H-C Flemming T RNeu andD JWozniak ldquoTheEPSmatrixthe ldquoHouse of Biofilm Cellsrdquordquo Journal of Bacteriology vol 189no 22 pp 7945ndash7947 2007

[22] I W Sutherland ldquoThe biofilm matrixmdashan immobilized butdynamic microbial environmentrdquo Trends in Microbiology vol9 no 5 pp 222ndash227 2001

[23] S S Branda S Vik L Friedman and R Kolter ldquoBiofilms thematrix revisitedrdquo Trends in Microbiology vol 13 no 1 pp 20ndash26 2005

[24] H-C Flemming and JWingender ldquoThe biofilmmatrixrdquoNatureReviews Microbiology vol 8 no 9 pp 623ndash633 2010

[25] J D Shrout D L Chopp C L Just M Hentzer M Givskovand M R Parsek ldquoThe impact of quorum sensing and swarm-ing motility on Pseudomonas aeruginosa biofilm formation isnutritionally conditionalrdquo Molecular Microbiology vol 62 no5 pp 1264ndash1277 2006

[26] M E Davey N C Caiazza and G A OrsquoToole ldquoRham-nolipid surfactant production affects biofilm architecture inPseudomonas aeruginosa PAO1rdquo Journal of Bacteriology vol185 no 3 pp 1027ndash1036 2003

[27] C Ryder M Byrd and D J Wozniak ldquoRole of polysaccha-rides inPseudomonas aeruginosa biofilmdevelopmentrdquoCurrentOpinion in Microbiology vol 10 no 6 pp 644ndash648 2007

[28] A Ghafoor I D Hay and B H A Rehm ldquoRole of exopolysac-charides in Pseudomonas aeruginosa biofilm formation andarchitecturerdquo Applied and Environmental Microbiology vol 77no 15 pp 5238ndash5246 2011

[29] L Ma M Conover H Lu M R Parsek K Bayles and DJ Wozniak ldquoAssembly and development of the Pseudomonasaeruginosa biofilmmatrixrdquo PLoS Pathogens vol 5 no 3 ArticleID e1000354 2009

[30] L Ma J Wang S Wang et al ldquoSynthesis of multiple Pseu-domonas aeruginosa biofilmmatrix exopolysaccharides is post-transcriptionally regulatedrdquo Environmental Microbiology vol14 no 8 pp 1995ndash2005 2012

[31] E E Mann and D J Wozniak ldquoPseudomonas biofilm matrixcomposition and niche biologyrdquo FEMS Microbiology Reviewsvol 36 no 4 pp 893ndash916 2012

[32] H Ertesvag and S Valla ldquoBiosynthesis and applications ofalginatesrdquo Polymer Degradation and Stability vol 59 no 1ndash3pp 85ndash91 1998

[33] I W Sutherland ldquoBiofilm exopolysaccharides a strong andsticky frameworkrdquoMicrobiology vol 147 no 1 pp 3ndash9 2001

[34] L Friedman and R Kolter ldquoGenes involved inmatrix formationin Pseudomonas aeruginosa PA14 biofilmsrdquoMolecular Microbi-ology vol 51 no 3 pp 675ndash690 2004

[35] M J Franklin D E Nivens J T Weadge and P LynneHowell ldquoBiosynthesis of the Pseudomonas aeruginosa extra-cellular polysaccharides alginate Pel and Pslrdquo Frontiers inMicrobiology vol 167 no 2 pp 1ndash16 2011

[36] M S Byrd I Sadovskaya E Vinogradov et al ldquoGeneticand biochemical analyses of the Pseudomonas aeruginosa Pslexopolysaccharide reveal overlapping roles for polysaccharidesynthesis enzymes in Psl and LPS productionrdquo MolecularMicrobiology vol 73 no 4 pp 622ndash638 2009

[37] K M Colvin V D Gordon K Murakami et al ldquoThe pel poly-saccharide can serve a structural and protective role in the bio-filmmatrix of Pseudomonas aeruginosardquo PLoS Pathogens vol 7no 1 Article ID e1001264 2011


[38] P Vasseur I Vallet-Gely C Soscia S Genin and A FillouxldquoThe pel genes of the Pseudomonas aeruginosa PAK strain areinvolved at early and late stages of biofilm formationrdquo Micro-biology vol 151 no 3 pp 985ndash997 2005

[39] J J T M Swartjes T Das S Sharifi et al ldquoA functional DNasei coating to prevent adhesion of bacteria and the formationof biofilmrdquo Advanced Functional Materials vol 23 no 22 pp2843ndash2849 2013

[40] L Yang K B Barken M E Skindersoe A B Christensen MGivskov and T Tolker-Nielsen ldquoEffects of iron on DNA releaseand biofilm development by Pseudomonas aeruginosardquo Micro-biology vol 153 no 5 pp 1318ndash1328 2007

[41] E S Gloag L Turnbull A Huang et al ldquoSelf-organization ofbacterial biofilms is facilitated by extracellular DNArdquo Proceed-ings of the National Academy of Sciences of the United States ofAmerica vol 110 no 28 pp 11541ndash11546 2013

[42] M Allesen-Holm K B Barken L Yang et al ldquoA characteriza-tion of DNA release in Pseudomonas aeruginosa cultures andbiofilmsrdquo Molecular Microbiology vol 59 no 4 pp 1114ndash11282006

[43] C B Whitchurch T Tolker-Nielsen P C Ragas and J SMattick ldquoExtracellular DNA required for bacterial biofilmformationrdquo Science vol 295 no 5559 p 1487 2002

[44] S E Finkel and R Kolter ldquoDNA as a nutrient novel role forbacterial competence gene homologsrdquo Journal of Bacteriologyvol 183 no 21 pp 6288ndash6293 2001

[45] H Mulcahy L Charron-Mazenod and S Lewenza ldquoPseu-domonas aeruginosa produces an extracellular deoxyribonucle-ase that is required for utilization of DNA as a nutrient sourcerdquoEnvironmental Microbiology vol 12 no 6 pp 1621ndash1629 2010

[46] T Kohler L K Curty F Barja C van Delden and J-CPechere ldquoSwarming of Pseudomonas aeruginosa is dependenton cell-to-cell signaling and requires flagella and pilirdquo Journalof Bacteriology vol 182 no 21 pp 5990ndash5996 2000

[47] J S Mattick ldquoType IV pili and twitching motilityrdquo AnnualReview of Microbiology vol 56 pp 289ndash314 2002

[48] E Deziel F Lepine S Milot and R Villemur ldquorhlA isrequired for the production of a novel biosurfactant promotingswarming motility in Pseudomonas aeruginosa 3-(3-hydro-xyalkanoyloxy)alkanoic acids (HAAs) the precursors of rham-nolipidsrdquoMicrobiology vol 149 no 8 pp 2005ndash2013 2003

[49] G A OrsquoToole and R Kolter ldquoFlagellar and twitching motilityare necessary for Pseudomonas aeruginosa biofilm develop-mentrdquoMolecular Microbiology vol 30 no 2 pp 295ndash304 1998

[50] S Ruer S Stender A Filloux and S De Bentzmann ldquoAssemblyof fimbrial structures in Pseudomonas aeruginosa functionalityand specificity of chaperone-ushermachineriesrdquo Journal of Bac-teriology vol 189 no 9 pp 3547ndash3555 2007

[51] K B Barken S J Pamp L Yang et al ldquoRoles of type IVpili flagellum-mediated motility and extracellular DNA in theformation of mature multicellular structures in Pseudomonasaeruginosa biofilmsrdquo Environmental Microbiology vol 10 no 9pp 2331ndash2343 2008

[52] T R De Kievit ldquoQuorum sensing in Pseudomonas aeruginosabiofilmsrdquo Environmental Microbiology vol 11 no 2 pp 279ndash288 2009

[53] M R Parsek and E P Greenberg ldquoSociomicrobiology theconnections between quorum sensing and biofilmsrdquo Trends inMicrobiology vol 13 no 1 pp 27ndash33 2005

[54] P N Jimenez G Koch J A Thompson K B Xavier RH Cool and W J Quax ldquoThe multiple signaling systems

regulating virulence in Pseudomonas aeruginosardquoMicrobiologyand Molecular Biology Reviews vol 76 no 1 pp 46ndash65 2012

[55] D G Davies M R Parsek J P Pearson B H Iglewski J WCosterton and E P Greenberg ldquoThe involvement of cell-to-cellsignals in the development of a bacterial biofilmrdquo Science vol280 no 5361 pp 295ndash298 1998

[56] K B Gilbert T H Kim R Gupta E P Greenberg and MSchuster ldquoGlobal position analysis of the Pseudomonas aerug-inosa quorum-sensing transcription factor LasRrdquo MolecularMicrobiology vol 73 no 6 pp 1072ndash1085 2009

[57] Y Sakuragi and R Kolter ldquoQuorum-sensing regulation of thebiofilm matrix genes (pel) of Pseudomonas aeruginosardquo Journalof Bacteriology vol 189 no 14 pp 5383ndash5386 2007

[58] GM Fraser andCHughes ldquoSwarmingmotilityrdquoCurrentOpin-ion in Microbiology vol 2 no 6 pp 630ndash635 1999

[59] R M Harshey ldquoBees arenrsquot the only ones swarming in gram-negative bacteriardquo Molecular Microbiology vol 13 no 3 pp389ndash394 1994

[60] R Daniels J Vanderleyden and J Michiels ldquoQuorum sens-ing and swarming migration in bacteriardquo FEMS MicrobiologyReviews vol 28 no 3 pp 261ndash289 2004

[61] GM Patriquin E Banin C Gilmour R Tuchman E P Green-berg and K Poole ldquoInfluence of quorum sensing and ironon twitching motility and biofilm formation in Pseudomonasaeruginosardquo Journal of Bacteriology vol 190 no 2 pp 662ndash6712008

[62] M Van Gennip L D Christensen M Alhede et al ldquoInactiva-tion of the rhlA gene in Pseudomonas aeruginosa preventsrhamnolipid production disabling the protection against poly-morphonuclear leukocytesrdquo Acta Pathologica Microbiologica et Immunologica Scandinavica vol 117 no 7 pp 537ndash546 2009

[63] D H Dusane S S Zinjarde V P Venugopalan R J C McleanM M Weber and P K S M Rahman ldquoQuorum sensingimplications on Rhamnolipid biosurfactant productionrdquo Bio-technology andGenetic Engineering Reviews vol 27 pp 159ndash1842010

[64] S J Pamp and T Tolker-Nielsen ldquoMultiple roles of biosurfac-tants in structural biofilmdevelopment byPseudomonas aerugi-nosardquo Journal of Bacteriology vol 189 no 6 pp 2531ndash2539 2007

[65] B R Boles MThoendel and P K Singh ldquoRhamnolipids medi-ate detachment of Pseudomonas aeruginosa from biofilmsrdquoMolecular Microbiology vol 57 no 5 pp 1210ndash1223 2005

[66] S R Schooling U K Charaf D G Allison and P Gilbert ldquoArole for rhamnolipid in biofilm dispersionrdquo Biofilms vol 1 pp91ndash99 2004

[67] S P Diggle R E Stacey C Dodd M Camara P Williams andK Winzer ldquoThe galactophilic lectin LecA contributes to bio-film development in Pseudomonas aeruginosardquo EnvironmentalMicrobiology vol 8 no 6 pp 1095ndash1104 2006

[68] D Tielker S Hacker R Loris et al ldquoPseudomonas aeruginosalectin LecB is located in the outer membrane and is involved inbiofilm formationrdquo Microbiology vol 151 no 5 pp 1313ndash13232005

[69] K Winzer C Falconer N C Garber S P Diggle M Camaraand P Williams ldquoThe Pseudomonas aeruginosa lectins PA-ILand PA-IIL are controlled by quorum sensing and by RpoSrdquoJournal of Bacteriology vol 182 no 22 pp 6401ndash6411 2000

[70] A Rodrigue Y Quentin A Lazdunski V Mejean and MFoglino ldquoTwo-component systems in Pseudomonas aeruginosawhy so manyrdquo Trends in Microbiology vol 8 no 11 pp 498ndash504 2000


[71] M D Parkins H Ceri and D G Storey ldquoPseudomonas aerug-inosa GacA a factor in multihost virulence is also essential forbiofilm formationrdquo Molecular Microbiology vol 40 no 5 pp1215ndash1226 2001

[72] A Brencic K A McFarland H R McManus et al ldquoThe GacSGacA signal transduction system of Pseudomonas aeruginosaacts exclusively through its control over the transcriptionof the RsmY and RsmZ regulatory small RNAsrdquo MolecularMicrobiology vol 73 no 3 pp 434ndash445 2009

[73] A Brencic and S Lory ldquoDetermination of the regulon and iden-tification of novel mRNA targets of Pseudomonas aeruginosaRsmArdquoMolecularMicrobiology vol 72 no 3 pp 612ndash632 2009

[74] Y Irie M Starkey A N Edwards D J Wozniak T Romeoand M R Parsek ldquoPseudomonas aeruginosa biofilm matrixpolysaccharide Psl is regulated transcriptionally by RpoS andpost-transcriptionally by RsmArdquo Molecular Microbiology vol78 no 1 pp 158ndash172 2010

[75] E Kay B Humair V Denervaud et al ldquoTwo GacA-dependentsmall RNAs modulate the quorum-sensing response in Pseu-domonas aeruginosardquo Journal of Bacteriology vol 188 no 16pp 6026ndash6033 2006

[76] G Pessi F Williams Z Hindle et al ldquoThe global posttran-scriptional regulator RsmA modulates production of viru-lence determinants and Nmdashacylhomoserine lactones in Pseu-domonas aeruginosardquo Journal of Bacteriology vol 183 no 22pp 6676ndash6683 2002

[77] C Reimmann M Beyeler A Latifi et al ldquoThe global activatorGacA of Pseudomonas aeruginosa PAO positively controls theproduction of the autoinducer N-butyryl-homoserine lactoneand the formation of the virulence factors pyocyanin cyanideand lipaserdquo Molecular Microbiology vol 24 no 2 pp 309ndash3191997

[78] A L Goodman B Kulasekara A Rietsch D Boyd R S Smithand S Lory ldquoA signaling network reciprocally regulates genesassociated with acute infection and chronic persistence in Pseu-domonas aeruginosardquo Developmental Cell vol 7 no 5 pp 745ndash754 2004

[79] W Kong L Chen J Zhao et al ldquoHybrid sensor kinase PA1611in Pseudomonas aeruginosa regulates transitions between acuteand chronic infection through direct interaction with RetSrdquoMolecular Microbiology vol 88 no 4 pp 784ndash797 2013

[80] I Ventre A L Goodman I Vallet-Gely et al ldquoMultiple sensorscontrol reciprocal expression of Pseudomonas aeruginosa reg-ulatory RNA and virulence genesrdquo Proceedings of the NationalAcademy of Sciences of the United States of America vol 103 no1 pp 171ndash176 2006

[81] H Mikkelsen R McMullan and A Filloux ldquoThe Pseudomonasaeruginosa reference strain PA14 displays increased virulencedue to a mutation in ladSrdquo PLoS ONE vol 6 no 12 Article IDe29113 2011

[82] A L Goodman M Merighi M Hyodo I Ventre A Fillouxand S Lory ldquoDirect interaction between sensor kinase proteinsmediates acute and chronic disease phenotypes in a bacterialpathogenrdquo Genes and Development vol 23 no 2 pp 249ndash2592009

[83] A R Records and D C Gross ldquoSensor kinases RetS and LadSregulate Pseudomonas syringae type VI secretion and virulencefactorsrdquo Journal of Bacteriology vol 192 no 14 pp 3584ndash35962010

[84] J W Hickman D F Tifrea and C S Harwood ldquoA chemosen-sory system that regulates biofilm formation through modu-lation of cyclic diguanylate levelsrdquo Proceedings of the National

Academy of Sciences of the United States of America vol 102 no40 pp 14422ndash14427 2005

[85] MMerighi V T LeeMHyodo YHayakawa and S Lory ldquoThesecond messenger bis-(31015840-51015840)-cyclic-GMP and its PilZ domain-containing receptor Alg44 are required for alginate biosynthesisin Pseudomonas aeruginosardquo Molecular Microbiology vol 65no 4 pp 876ndash895 2007

[86] R Hengge ldquoPrinciples of c-di-GMP signalling in bacteriardquoNature Reviews Microbiology vol 7 no 4 pp 263ndash273 2009

[87] V T Lee J M Matewish J L Kessler M Hyodo Y Hayakawaand S Lory ldquoA cyclic-di-GMP receptor required for bacterialexopolysaccharide productionrdquoMolecularMicrobiology vol 65no 6 pp 1474ndash1484 2007

[88] C A Janeway Jr and R Medzhitov ldquoInnate immune recogni-tionrdquo Annual Review of Immunology vol 20 pp 197ndash216 2002

[89] T S Walker H P Bais E Deziel et al ldquoPseudomonas aerugi-nosa- plant root interactions Pathogenicity biofilm formationand root exudationrdquo Plant Physiology vol 134 no 1 pp 320ndash331 2004

[90] J D G Jones and J L Dangl ldquoThe plant immune systemrdquoNature vol 444 no 7117 pp 323ndash329 2006

[91] U Mathesius S Mulders M Gao et al ldquoExtensive and specificresponses of a eukaryote to bacterial quorum-sensing signalsrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 100 no 3 pp 1444ndash1449 2003

[92] AHartmann andA Schikora ldquoQuorum sensing of bacteria andtrans-kingdom interactions ofN-acyl homoserine lactoneswitheukaryotesrdquo Journal of Chemical Ecology vol 38 no 6 pp 704ndash713 2012

[93] AHartmannMRothballer BAHense andP Schroder ldquoBac-terial quorum sensing compounds are important modulatorsof microbe-plant interactionsrdquo Frontiers in Plant Science vol 5article 131 2014

[94] M G Kociolek ldquoQuorum-sensing inhibitors and biofilmsrdquoAnti-Infective Agents in Medicinal Chemistry vol 8 no 4 pp315ndash326 2009

[95] W R J D Galloway J T Hodgkinson S Bowden M Welchand D R Spring ldquoApplications of small molecule activatorsand inhibitors of quorum sensing in Gram-negative bacteriardquoTrends in Microbiology vol 20 no 9 pp 449ndash458 2012

[96] B LaSarre and M J Federle ldquoExploiting quorum sensingto confuse bacterial pathogensrdquo Microbiology and MolecularBiology Reviews vol 77 no 1 pp 73ndash111 2013

[97] G D Geske R J Wezeman A P Siegel and H E BlackwellldquoSmall molecule inhibitors of bacterial quorum sensing andbiofilm formationrdquo Journal of the American Chemical Societyvol 127 no 37 pp 12762ndash12763 2005

[98] K M Smith Y Bu and H Suga ldquoLibrary screening forsynthetic agonists and antagonists of a Pseudomonas aeruginosaautoinducerrdquo Chemistry and Biology vol 10 no 6 pp 563ndash5712003

[99] T Ishida T Ikeda N Takiguchi A Kuroda H Ohtake andJ Kato ldquoInhibition of quorum sensing in Pseudomonas aerugi-nosa by N-acyl cyclopentylamidesrdquo Applied and EnvironmentalMicrobiology vol 73 no 10 pp 3183ndash3188 2007

[100] M Hentzer K Riedel T B Rasmussen et al ldquoInhibition ofquorum sensing in Pseudomonas aeruginosa biofilm bacteria bya halogenated furanone compoundrdquoMicrobiology vol 148 no1 pp 87ndash102 2002

[101] M Hentzer H Wu J B Andersen et al ldquoAttenuation of Pseu-domonas aeruginosa virulence by quorum sensing inhibitorsrdquoEMBO Journal vol 22 no 15 pp 3803ndash3815 2003


[102] HWu Z Song M Givskov and N Hoslashiby ldquoEffects of quorum-sensing on immunoglobulin G responses in a rat model ofchronic lung infection with Pseudomonas aeruginosardquoMicrobesand Infection vol 6 no 1 pp 34ndash37 2004

[103] M E Skindersoe M Alhede R Phipps et al ldquoEffects of anti-biotics on quorum sensing in Pseudomonas aeruginosardquo Anti-microbial Agents and Chemotherapy vol 52 no 10 pp 3648ndash3663 2008

[104] K Tateda R Comte J-C Pechere T Kohler K Yamaguchi andC van Delden ldquoAzithromycin inhibits quorum sensing in Pseu-domonas aeruginosardquo Antimicrobial Agents and Chemotherapyvol 45 no 6 pp 1930ndash1933 2001

[105] T Ichimiya K Takeoka K Hiramatsu K Hirai T YamasakiandMNasu ldquoThe influence of azithromycin on the biofilm for-mation of Pseudomonas aeruginosa in vitrordquoChemotherapy vol42 no 3 pp 186ndash191 1996

[106] J C Pechere ldquoAzithromycin reduces the production of viru-lence factors in Pseudomonas aeruginosa by inhibiting quorumsensingrdquo Japanese Journal of Antibiotics vol 54 pp 87ndash89 2001

[107] D Sofer N Gilboa-Garber A Belz and N C Garber ldquorsquoSub-inhibitoryrsquo erythromycin represses production of Pseudomonasaeruginosa lectins autoinducer and virulence factorsrdquo Chem-otherapy vol 45 no 5 pp 335ndash341 1999

[108] S Favre-Bonte T Kohler and C van Delden ldquoBiofilm forma-tion by Pseudomonas aeruginosa role of the C4-HSL cell-to-cellsignal and inhibition by azithromycinrdquo Journal of AntimicrobialChemotherapy vol 52 no 4 pp 598ndash604 2003

[109] I Perez-Martınez and D Haas ldquoAzithromycin inhibits expres-sion of the GacA-dependent small RNAs RsmY and RsmZin Pseudomonas aeruginosardquo Antimicrobial Agents and Chem-otherapy vol 55 no 7 pp 3399ndash3405 2011

[110] A Bala R Kumar and K Harjai ldquoInhibition of quorumsensing in Pseudomonas aeruginosa by azithromycin and itseffectiveness in urinary tract infectionsrdquo Journal of MedicalMicrobiology vol 60 no 3 pp 300ndash306 2011

[111] T B Rasmussen M E Skindersoe T Bjarnsholt et al ldquoIdentityand effects of quorum-sensing inhibitors produced by Penicil-lium speciesrdquoMicrobiology vol 151 no 5 pp 1325ndash1340 2005

[112] N Glaser andH Stopper ldquoPatulin mechanism of genotoxicityrdquoFood andChemical Toxicology vol 50 no 5 pp 1796ndash1801 2012

[113] M E Skindersoe P Ettinger-Epstein T B Rasmussen T Bjarn-sholt R de Nys andM Givskov ldquoQuorum sensing antagonismfrommarine organismsrdquoMarine Biotechnology vol 10 no 1 pp56ndash63 2008

[114] S S Ebada W Lin and P Proksch ldquoBioactive sesterterpenesand triterpenes frommarine sponges occurrence and pharma-cological significancerdquoMarine Drugs vol 8 no 2 pp 313ndash3462010

[115] J Park G F Kaufmann J P Bowen J L Arbiser and KD Janda ldquoSolenopsin A a venom alkaloid from the fireant Solenopsis invicta inhibits quorum-sensing signaling inPseudomonas aeruginosardquo Journal of Infectious Diseases vol198 no 8 pp 1198ndash1201 2008

[116] E A Ozer A Pezzulo D M Shih et al ldquoHuman and murineparaoxonase 1 are host modulators of Pseudomonas aeruginosaquorum-sensingrdquo FEMSMicrobiology Letters vol 253 no 1 pp29ndash37 2005

[117] F Yang L-H Wang J Wang Y-H Dong Y H Jiang andL-H Zhang ldquoQuorum quenching enzyme activity is widelyconserved in the sera of mammalian speciesrdquo FEBS Letters vol579 no 17 pp 3713ndash3717 2005

[118] T Rudrappa and H P Bais ldquoCurcumin a known phenolicfrom Curcuma longa attenuates the virulence of Pseudomonasaeruginosa PAO1 in whole plant and animal pathogenicitymodelsrdquo Journal of Agricultural and Food Chemistry vol 56 no6 pp 1955ndash1962 2008

[119] A Annapoorani V Umamageswaran R Parameswari S KPandian and A V Ravi ldquoComputational discovery of putativequorum sensing inhibitors against LasR and RhlR receptorproteins of Pseudomonas aeruginosardquo Journal of Computer-Aided Molecular Design vol 26 no 9 pp 1067ndash1077 2012

[120] S Sarabhai P Sharma and N Capalash ldquoEllagic acid deriva-tives from Terminalia chebula Retz Downregulate the expres-sion of quorum sensing genes to attenuate Pseudomonas aerugi-nosa PAO1 virulencerdquo PLoSONE vol 8 no 1 Article ID e534412013

[121] B Girennavar M L Cepeda K A Soni et al ldquoGrapefruitjuice and its furocoumarins inhibits autoinducer signaling andbiofilm formation in bacteriardquo International Journal of FoodMicrobiology vol 125 no 2 pp 204ndash208 2008

[122] Z Zeng L Qian L Cao et al ldquoVirtual screening for novelquorum sensing inhibitors to eradicate biofilm formation ofPseudomonas aeruginosardquoAppliedMicrobiology and Biotechnol-ogy vol 79 no 1 pp 119ndash126 2008

[123] X Ding B Yin L Qian et al ldquoScreening for novel quorum-sensing inhibitors to interfere with the formation of Pseu-domonas aeruginosa biofilmrdquo Journal of Medical Microbiologyvol 60 part 12 pp 1827ndash1834 2011

[124] O M Vandeputte M Kiendrebeogo S Rajaonson et alldquoIdentification of catechin as one of the flavonoids from com-bretum albiflorum bark extract that reduces the production ofquorum-sensing-controlled virulence factors in PseudomonasaeruginosaPAQ1rdquoApplied andEnvironmentalMicrobiology vol76 no 1 pp 243ndash253 2010

[125] O M Vandeputte M Kiendrebeogo T Rasamiravaka et alldquoThe flavanone naringenin reduces the production of quorumsensing-controlled virulence factors in pseudomonas aerugi-nosa PAO1rdquoMicrobiology vol 157 no 7 pp 2120ndash2132 2011

[126] T Rasamiravaka A Jedrzejowski M Kiendrebeogo et alldquoEndemic Malagasy Dalbergia species inhibit quorum sensingin Pseudomonas aeruginosa PAO1rdquoMicrobiology vol 159 no 5pp 924ndash938 2013

[127] C A Ta M Freundorfer T F Mah et al ldquoInhibition of bac-terial quorum sensing and biofilm formation by extracts of neo-tropical rainforest plantsrdquo PlantaMedica vol 80 no 4 pp 343ndash350 2014

[128] L Zhou H Zheng Y Tang W Yu and Q Gong ldquoEugenolinhibits quorum sensing at sub-inhibitory concentrationsrdquoBiotechnology Letters vol 35 no 4 pp 631ndash637 2013

[129] F M Husain I Ahmad M Asif and Q Tahseen ldquoInfluenceof clove oil on certain quorum-sensing-regulated functions andbiofilm of Pseudomonas aeruginosa andAeromonas hydrophilardquoJournal of Biosciences vol 38 no 5 pp 835ndash844 2013

[130] T H Jakobsen M van Gennip R K Phipps et al ldquoAjoene asulfur-rich molecule from garlic inhibits genes controlled byquorum sensingrdquo Antimicrobial Agents and Chemotherapy vol56 no 5 pp 2314ndash2325 2012

[131] N C Cady K A McKean J Behnke et al ldquoInhibition ofbiofilm formation quorum sensing and infection in Pseu-domonas aeruginosa by natural products-inspired organosulfurcompoundsrdquo PLoS ONE vol 7 no 6 Article ID e38492 2012


[132] R W Huigens III J J Richards G Parise et al ldquoInhibition ofPseudomonas aeruginosa biofilm formation with bromoagelif-erin analoguesrdquo Journal of the American Chemical Society vol129 no 22 pp 6966ndash6967 2007

[133] J J Richards T E Ballard R W Huigens III and C MelanderldquoSynthesis and screening of an oroidin library against Pseu-domonas aeruginosa biofilmsrdquo ChemBioChem vol 9 no 8 pp1267ndash1279 2008

[134] M A Alkawash J S Soothill and N L Schiller ldquoAlginate lyaseenhances antibiotic killing of mucoid Pseudomonas aeruginosain biofilmsrdquo Acta Pathologica Microbiologica et ImmunologicaScandinavica vol 114 no 2 pp 131ndash138 2006

[135] J W Lampp and K E Griswold ldquoAlginate lyase exhibits cata-lysis-independent biofilm dispersion and antibiotic synergyrdquoAntimicrobial Agents and Chemotherapy vol 57 no 1 pp 137ndash145 2013

[136] L Eckhart H Fischer K B Barken T Tolker-Nielsen and ETschachler ldquoDnase1L2 suppresses biofilm formation by Pseu-domonas aeruginosa and Staphylococcus aureusrdquo British Journalof Dermatology vol 156 no 6 pp 1342ndash1345 2007

[137] G V Tetz N K Artemenko and V V Tetz ldquoEffect of DNaseand antibiotics on biofilm characteristicsrdquo Antimicrobial Agentsand Chemotherapy vol 53 no 3 pp 1204ndash1209 2009

[138] H-S Kim and H-D Park ldquoGinger extract inhibits biofilmformation by Pseudomonas aeruginosa PA14rdquo PLoS ONE vol8 no 9 Article ID e76106 2013

[139] L Kumar S Chhibber andKHarjai ldquoZingerone inhibit biofilmformation and improve antibiofilm efficacy of ciprofloxacinagainst Pseudomonas aeruginosa PAO1rdquo Fitoterapia vol 90 pp73ndash78 2013

[140] V A Carneiro H S Dos Santos F V S Arruda et al ldquoCasbanediterpene as a promising natural antimicrobial agent againstbiofilm-associated infectionsrdquoMolecules vol 16 no 1 pp 190ndash201 2011

[141] D Ren R Zuo A F Gonzalez-Barrios et al ldquoDifferential geneexpression for investigation of Escherichia coli biofilm inhibi-tion by plant extract ursolic acidrdquo Applied and EnvironmentalMicrobiology vol 71 no 7 pp 4022ndash4034 2005

[142] J-F Hu E Garo M G Goering et al ldquoBacterial biofilm inhib-itors fromDiospyros dendordquo Journal of Natural Products vol 69no 1 pp 118ndash120 2006

[143] M I Gomez and A Prince ldquoOpportunistic infections in lungdisease Pseudomonas infections in cystic fibrosisrdquo CurrentOpinion in Pharmacology vol 7 no 3 pp 244ndash251 2007

[144] T Bjarnsholt K Kirketerp-Moslashller P Oslash Jensen et al ldquoWhychronic wounds will not heal a novel hypothesisrdquo WoundRepair and Regeneration vol 16 no 1 pp 2ndash10 2008

[145] T Hoslashgsberg T Bjarnsholt J S Thomsen and K Kirketerp-Moslashller ldquoSuccess rate of split-thickness skin grafting of chronicvenous leg ulcers depends on the presence of Pseudomonasaeruginosa a retrospective studyrdquo PLoS ONE vol 6 no 5Article ID e20492 2011

[146] T SWalker K L Tomlin G SWorthen et al ldquoEnhanced Pseu-domonas aeruginosa biofilm development mediated by humanneutrophilsrdquo Infection and Immunity vol 73 no 6 pp 3693ndash3701 2005

[147] W-C Chiang M Nilsson P Oslash Jensen et al ldquoExtracellularDNA shields against aminoglycosides in Pseudomonas aerugi-nosa biofilmsrdquo Antimicrobial Agents and Chemotherapy vol 57no 5 pp 2352ndash2361 2013

[148] B Mellbye and M Schuster ldquoThe sociomicrobiology of antivir-ulence drug resistance a proof of conceptrdquo mBio vol 2 no 52011

[149] A R Smyth P M Cifelli C A Ortori et al ldquoGarlic asan inhibitor of Pseudomonas aeruginosa quorum sensing incystic fibrosismdasha pilot randomized controlled trialrdquo PediatricPulmonology vol 45 no 4 pp 356ndash362 2010

[150] R T LaLonde L Bu A Henwood J Fiumano and LZhang ldquoBromine- chlorine- and mixed halogen-substituted4-methyl-2(5H)-furanones synthesis and mutagenic effects ofhalogen and hydroxyl group replacementsrdquo Chemical Researchin Toxicology vol 10 no 12 pp 1427ndash1436 1997

[151] Y Kim N-H Nam Y-J You and B-Z Ahn ldquoSynthesisand cytotoxicity of 34-diaryl-2(5H)-furanonesrdquo Bioorganic andMedicinal Chemistry Letters vol 12 no 4 pp 719ndash722 2002

[152] A Beury-Cirou M Tannieres C Minard et al ldquoAt a supra-physiological concentration human sexual hormones act asquorum-sensing inhibitorsrdquo PLoS ONE vol 8 no 12 ArticleID e83564 2013

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of


Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 2014

Zoology


Molecular Biology International

GenomicsInternational Journal of


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014


BioinformaticsAdvances in

Marine BiologyJournal of



Signal TransductionJournal of


BioMed Research International

Evolutionary BiologyInternational Journal of



Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014


Genetics Research International


Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational



Enzyme Research



Microbiology


(b)(a)

Stage I

(c) (d) (e)

Stage II Stage III Stage IV Stage V

EPSBacteria

25120583m

8h 14h 1ndash4days 5days

1day 2days 3days 4days

2h

Figure 1 Biofilm lifestyle cycle of P aeruginosa PAO1 grown in glucose minimal media In stage I planktonic bacteria initiate attachment toan abiotic surface which becomes irreversible in stage II Stage III corresponds to microcolony formation Stage IV corresponds to biofilmmaturation and growth of the three-dimensional community Dispersion occurs in stage V and planktonic bacteria that are released fromthe biofilm to colonize other sites The biofilm formation by P aeruginosa PAO1 was revealed with Syto9 and visualized in Leica DM IRE2inverted fluorescence microscope with 400x magnification at 2 h (Stage I) 8 h (Stage II) 14 h (Stage III) 1 to 4 days (Stage IV) and 5 days(Stage V) Images represent a 250 times 250-120583m field

interaction including quorum sensing (QS) pathways will besummarized

2 Biofilm Lifestyle Cycle of P aeruginosa

Biofilm formation is an endless cycle in which organizedcommunities of bacteria are encased in a matrix of extra-cellular polymeric substances (EPS) that hold microbialcells together to a surface [14 15] these are thought to bedeterminant in 65ndash80 of all microbial infections [16ndash18] Inthis microscopic world biofilms are metaphorically called aldquocity of microbesrdquo [19 20] with EPS which represents 85 oftotal biofilm biomass as ldquohouse of the biofilm cellsrdquo [21] EPSis composed mainly of biomolecules exopolysaccharidesextracellular DNA (eDNA) and polypeptides that form

a highly hydrated polarmixture that contributes to the overallstructural scaffold and architecture of the biofilm [22ndash24]

Depending on P aeruginosa strains andor nutritionalconditions different biofilm phenotypes can be developed[25] For instance in glucose minimal media biofilm lifestylecycle of P aeruginosa PAO1 can be subdivided into fivemajor phenotypic steps (Figure 1) The process begins by thereversible adhesion of planktonic bacteria onto a surface suit-able for growth (Figure 1(a) Stage I) followed by irreversibleattachment of bacteria which thereafter form microcoloniesin EPS matrix (Figure 1(b) Stage II) Progressively bacterialmicrocolonies expand and their confluences lead to a morestructured phenotype with noncolonized space (Figure 1(c)Stage III) Then noncolonized spaces are filled with bacteriawhich finally cover the entire surface (Figure 1(d) Stage IV)














c-di-GMP


Swarming Twitching



1

2

3

GacSRetS LadSP

Input signal(s)

GacAP

RsmA

RsmZY

+ rsmA

GacA

RR

RR


LasR3-oxo-C12-HSL

RhlRC4-HSL

RhlILasI

PQS system







ON

HO

O

ON

HO

O O

C4-HSL

3-Oxo-C12-HSL

(a) Native AHLs





NH

N

N

H

H H

O

O

NH

OnO

O

OO

NH H O

OO

Br

C9H19

(b) AHLs analogues



Manoalide

O

O O

OO

O

O

XH

OOH

OH

Br

OO

O

OH

HO























compo

unds

forP

aeruginosabiofi

lmform

ation

Naturalprod

uctscompo

unds

Orig

inClass

Activ

ities

References

QSinhibitio

nBiofi

lminhibitio

n(a)

Disp

ersio

nprom

otion

Synergywith

antib

iotic

Alginatelyase

Paeruginosa

Enzyme

minus+

++(1)

[134]

Ursolicacid

Diospyros

dend

oWelw

Triterpenoid

minus+(24h

)motility

NC

NC

[141]

p-Cou

maroyl-h

ydroxy-ursolicacid

Diospyros

dend

oWelw

Cou

maratee

stero

ftriterpene

NC

+(24h

)NC

NC

[142]

Zingeron

eZingiberoffi

cinaleR

osc

Phenoliccompo

und

NC

+(168

h)c-di-G

MP

NC

+(2)

[138139]

Casbaned

iterpene

Croton

nepetaefo

liusB

aill

Diterpenoid

NC

+(24h

)adherence

NC

NC

[140]

DNaseI

Bovine

pancreas

Enzyme

NC

+(18ndash24

h)+

+(3)

[137]

DNase-1L2

Hum

anstratum

corneum

[136]

Paraoxon

ases

1Hum

anandmurines

era

Enzyme(lacton

ase)

++(24h

)NC

NC

[116117]

Manoalid

eLu

ffarie

llavaria

bilis

(Polejaeff

1884)

(marineo

rganism

)Seste

rterpeno

id+(la

ssystem)

+(24h

)NC

NC

[113114]

Soleno

psin

ASolen

opsis

invicta(in

sectant)

Alkaloid

+(rhlsyste

m)

+(24h

)NC

NC

[115]

Catechin

Combretum

albiflorum

(Tul)Jong

kind

Flavon

oid

+(la

srhlsyste

ms)

+(24h

)NC

NC

[124]

Naringenin

Com

mercial

Flavon

oid

+(la

srhlsyste

ms)

+(48h

)NC

NC

[125]

Cou

maratee

ster

Dtrichocarpa

Baker

Phenoliccompo

und

+(la

srhlsyste

ms)

+(48h

)+

+(1)

[126]

Ajoene

Alliu

msativ

umL

Organosulfur

+(la

srhlsyste

ms)

+(96h

)NC

+(1)

[130]

Ellagica

cidderiv

atives

Term

inaliachebulaRe

tz

Phenoliccompo

und

+(la

srhlsyste

ms)

+(72h

)NC

+(1)

[120]

Rosm

arinicacid

Ocim

umbasilicu

mL

Phenoliccompo

und

+(la

srhlsyste

ms)

+(18h

)minus

NC

[89119

]

Eugeno

lSyzygium

arom

aticu

m(L)

MerrEt

Perry

Phenylprop

anoid

+(la

spqs

syste

ms)

+(24h

)NC

NC

[128]

Curcum

inCu

rcum

alongaL

Phenoliccompo

und

+(A

HLs)

+(48h

)NC

NC

[118]

Bergam

ottin

and


Citru

sparadisi

Macfad

(Rio

RedandMarsh

Whitegrapefruits)

Furocoum

arins

+(A

I-1and

AI-2)

+(24h

)NC

NC

[121]

Penicillica

cid

Penicilliu

mspecies

Furano

ne+(LasR

RhlR)

NC

NC

NC

[111]

Patulin

Furopyrano

ne+(LasRRh

lR)

mdashDagger

NC

+(1)

Emod

inRh

eum

palm

atum

LAnthraquino

ne+(docking

traR

)+(72h

)NC

+(3)

[123]

Baicalein

Scutellariabaica

lensis

Georgi

Flavon

oid

+(docking

traR

)+(72h

)NC

+(3)

[122]

+yesminusnoNC

notcom

mun

icated

DaggerPatulin

does

notaffectthed

evelo

pmento

fbiofilm

(a) Exp

erim

entd

uration

(1) A

minoglycosid

es(2)ciprofl

oxacin(3)am

picillin


Table2Synthetic

inhibitory

compo

unds

inPaeruginosa

biofi

lmform

ation

Synthetic

compo

unds

(Naturalcompo

undorigin)

Activ

ities

References

QSinhibitio

nBiofi

lminhibitio

n(a)

Disp

ersio

nprom

otion

Synergisticantib

iotic

andor

immun

edefense

effect

TAGEandCA

GE(Bromoageliferin)

NC

+(24h

)+

NC

[132]

Dihydrosventrin

(Sventrin

)NC

+(24h

)+

NC

[133]

N-(4-brom

o-ph

enylacetanoyl)-l-H

SL

N-(indo


(AHLs)

+AHLs

antagonist(la

ssystem)

+(24h

)NC

NC

[97]

3-oxo-C1

2-cyclo

hexano

ne(A

HLs)

+AHLs

antagonist(la

ssystem)

+(24h

)NC

NC

[98]

C10-cyclo

pentylam

ide(AHLs)

+(la

sIandrhlA)

+(24h

)NC

NC

[99]

Furano

neC-

30andC-

56(Furanon

e)+(la

srhlsystems)

+(24h

)[55100101]

S-ph


(Cysteinesulfoxide

alliin)

+(la

srhlsystems)

+(24h

)NC

NC

[148]

Diphenyld

isulfide

(Disu

lfide

deriv

atives

ofthea

lliinase

mediatedreactio

ns)

+lassystem

+(24h

)NC

NC

AzythromycinDagger

(Erythromycin)

+(gacA

lasa

ndrhlsystems)

+(72h

)+

+(1)

[103108109]

+yesminusnoNC

notcom

mun

icated

DaggerAt

subinh

ibito

ryconcentration

(a) Exp

erim

entd

uration

(1) A

minoglycosid

es


Curcumin Catechin

Bergamottin

Zingerone

Rosmarinic acid


Naringenin

Baicalein

Eugenol


HO

HO

HO

OHOH

OH

OHOH

OH

OH

OH

OH

OHO

OO

O

OO

O OHOH

OHOH

O

OR

O

HO

HOHO

HO

HO

HOHO

OH

OH

OH

O

O

O

O


O O O

O

O O

O

O

O O

O

OCH3

OCH3

OCH3 H3CO










Two-day old culture



(a) (b)






















Table3Factorsa

ffectingbiofi

lmlifestyleregu

latio

n

Biofi

lmlifestylecycle

StageI


StageII


StageIII

Maturation-1

(microcolony

developm

ent)

StageIV

Maturation-2

(maintenance)

StageV

Disp

ersio

n

Implicated

factors

c-di-G

MP

(i)Flagellaa

ndtype

IVpili

(ii)A

dhesins

(iii)PslPel


ication

lasI

(ii)T

ypeIVfim

briae

(iii)Matrix

compo

nentsPsl

PeleD

NA

(iv)L

ectin

AB

(v)rhlA


ication

(ii)M

atrix

compo

nentsPslPel

eDNA

(iii)rhlA

Rham

nolip

ids

Generaltarget

(i)Prom

otingplankton

iclifestyle

(ii)B

lockingsw

itchfro

mplankton

icto

biofi

lmlifestyle

Redu

cing

initialadhesio

nandinteraction

Interfe

ringwith

QS

commun

ication

(i)Re

activ

atingmetabolic

activ

ityfora

ntibiotic

efficiency

(ii)Interferin

gwith

QS

commun

ication

Prom

otingdispersio

nand

degradation

Exam

ples

ofextractsor

compo

unds

(i)Gingere

xtract

(ii)U

rsolicacid

(i)Ca

sbaned

iterpene

(ii)C

oumaratee

ster

Cou

maratee

ster

(i)Soleno

psin

A(ii)N

aringenin

(iii)Fu

rano

neC-

30and-56

(iv)F

lavan-3-olC

atechin

(v)A

joene

(vi)Cou

maratee

ster

DNAs

eI1L2


Acknowledgment


References






































































































































































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology














c-di-GMP


Swarming Twitching



1

2

3

GacSRetS LadSP

Input signal(s)

GacAP

RsmA

RsmZY

+ rsmA

GacA

RR

RR


LasR3-oxo-C12-HSL

RhlRC4-HSL

RhlILasI

PQS system







ON

HO

O

ON

HO

O O

C4-HSL

3-Oxo-C12-HSL

(a) Native AHLs





NH

N

N

H

H H

O

O

NH

OnO

O

OO

NH H O

OO

Br

C9H19

(b) AHLs analogues



Manoalide

O

O O

OO

O

O

XH

OOH

OH

Br

OO

O

OH

HO























compo

unds

forP

aeruginosabiofi

lmform

ation

Naturalprod

uctscompo

unds

Orig

inClass

Activ

ities

References

QSinhibitio

nBiofi

lminhibitio

n(a)

Disp

ersio

nprom

otion

Synergywith

antib

iotic

Alginatelyase

Paeruginosa

Enzyme

minus+

++(1)

[134]

Ursolicacid

Diospyros

dend

oWelw

Triterpenoid

minus+(24h

)motility

NC

NC

[141]

p-Cou

maroyl-h

ydroxy-ursolicacid

Diospyros

dend

oWelw

Cou

maratee

stero

ftriterpene

NC

+(24h

)NC

NC

[142]

Zingeron

eZingiberoffi

cinaleR

osc

Phenoliccompo

und

NC

+(168

h)c-di-G

MP

NC

+(2)

[138139]

Casbaned

iterpene

Croton

nepetaefo

liusB

aill

Diterpenoid

NC

+(24h

)adherence

NC

NC

[140]

DNaseI

Bovine

pancreas

Enzyme

NC

+(18ndash24

h)+

+(3)

[137]

DNase-1L2

Hum

anstratum

corneum

[136]

Paraoxon

ases

1Hum

anandmurines

era

Enzyme(lacton

ase)

++(24h

)NC

NC

[116117]

Manoalid

eLu

ffarie

llavaria

bilis

(Polejaeff

1884)

(marineo

rganism

)Seste

rterpeno

id+(la

ssystem)

+(24h

)NC

NC

[113114]

Soleno

psin

ASolen

opsis

invicta(in

sectant)

Alkaloid

+(rhlsyste

m)

+(24h

)NC

NC

[115]

Catechin

Combretum

albiflorum

(Tul)Jong

kind

Flavon

oid

+(la

srhlsyste

ms)

+(24h

)NC

NC

[124]

Naringenin

Com

mercial

Flavon

oid

+(la

srhlsyste

ms)

+(48h

)NC

NC

[125]

Cou

maratee

ster

Dtrichocarpa

Baker

Phenoliccompo

und

+(la

srhlsyste

ms)

+(48h

)+

+(1)

[126]

Ajoene

Alliu

msativ

umL

Organosulfur

+(la

srhlsyste

ms)

+(96h

)NC

+(1)

[130]

Ellagica

cidderiv

atives

Term

inaliachebulaRe

tz

Phenoliccompo

und

+(la

srhlsyste

ms)

+(72h

)NC

+(1)

[120]

Rosm

arinicacid

Ocim

umbasilicu

mL

Phenoliccompo

und

+(la

srhlsyste

ms)

+(18h

)minus

NC

[89119

]

Eugeno

lSyzygium

arom

aticu

m(L)

MerrEt

Perry

Phenylprop

anoid

+(la

spqs

syste

ms)

+(24h

)NC

NC

[128]

Curcum

inCu

rcum

alongaL

Phenoliccompo

und

+(A

HLs)

+(48h

)NC

NC

[118]

Bergam

ottin

and


Citru

sparadisi

Macfad

(Rio

RedandMarsh

Whitegrapefruits)

Furocoum

arins

+(A

I-1and

AI-2)

+(24h

)NC

NC

[121]

Penicillica

cid

Penicilliu

mspecies

Furano

ne+(LasR

RhlR)

NC

NC

NC

[111]

Patulin

Furopyrano

ne+(LasRRh

lR)

mdashDagger

NC

+(1)

Emod

inRh

eum

palm

atum

LAnthraquino

ne+(docking

traR

)+(72h

)NC

+(3)

[123]

Baicalein

Scutellariabaica

lensis

Georgi

Flavon

oid

+(docking

traR

)+(72h

)NC

+(3)

[122]

+yesminusnoNC

notcom

mun

icated

DaggerPatulin

does

notaffectthed

evelo

pmento

fbiofilm

(a) Exp

erim

entd

uration

(1) A

minoglycosid

es(2)ciprofl

oxacin(3)am

picillin


Table2Synthetic

inhibitory

compo

unds

inPaeruginosa

biofi

lmform

ation

Synthetic

compo

unds

(Naturalcompo

undorigin)

Activ

ities

References

QSinhibitio

nBiofi

lminhibitio

n(a)

Disp

ersio

nprom

otion

Synergisticantib

iotic

andor

immun

edefense

effect

TAGEandCA

GE(Bromoageliferin)

NC

+(24h

)+

NC

[132]

Dihydrosventrin

(Sventrin

)NC

+(24h

)+

NC

[133]

N-(4-brom

o-ph

enylacetanoyl)-l-H

SL

N-(indo


(AHLs)

+AHLs

antagonist(la

ssystem)

+(24h

)NC

NC

[97]

3-oxo-C1

2-cyclo

hexano

ne(A

HLs)

+AHLs

antagonist(la

ssystem)

+(24h

)NC

NC

[98]

C10-cyclo

pentylam

ide(AHLs)

+(la

sIandrhlA)

+(24h

)NC

NC

[99]

Furano

neC-

30andC-

56(Furanon

e)+(la

srhlsystems)

+(24h

)[55100101]

S-ph


(Cysteinesulfoxide

alliin)

+(la

srhlsystems)

+(24h

)NC

NC

[148]

Diphenyld

isulfide

(Disu

lfide

deriv

atives

ofthea

lliinase

mediatedreactio

ns)

+lassystem

+(24h

)NC

NC

AzythromycinDagger

(Erythromycin)

+(gacA

lasa

ndrhlsystems)

+(72h

)+

+(1)

[103108109]

+yesminusnoNC

notcom

mun

icated

DaggerAt

subinh

ibito

ryconcentration

(a) Exp

erim

entd

uration

(1) A

minoglycosid

es


Curcumin Catechin

Bergamottin

Zingerone

Rosmarinic acid


Naringenin

Baicalein

Eugenol


HO

HO

HO

OHOH

OH

OHOH

OH

OH

OH

OH

OHO

OO

O

OO

O OHOH

OHOH

O

OR

O

HO

HOHO

HO

HO

HOHO

OH

OH

OH

O

O

O

O


O O O

O

O O

O

O

O O

O

OCH3

OCH3

OCH3 H3CO










Two-day old culture



(a) (b)






















Table3Factorsa

ffectingbiofi

lmlifestyleregu

latio

n

Biofi

lmlifestylecycle

StageI


StageII


StageIII

Maturation-1

(microcolony

developm

ent)

StageIV

Maturation-2

(maintenance)

StageV

Disp

ersio

n

Implicated

factors

c-di-G

MP

(i)Flagellaa

ndtype

IVpili

(ii)A

dhesins

(iii)PslPel


ication

lasI

(ii)T

ypeIVfim

briae

(iii)Matrix

compo

nentsPsl

PeleD

NA

(iv)L

ectin

AB

(v)rhlA


ication

(ii)M

atrix

compo

nentsPslPel

eDNA

(iii)rhlA

Rham

nolip

ids

Generaltarget

(i)Prom

otingplankton

iclifestyle

(ii)B

lockingsw

itchfro

mplankton

icto

biofi

lmlifestyle

Redu

cing

initialadhesio

nandinteraction

Interfe

ringwith

QS

commun

ication

(i)Re

activ

atingmetabolic

activ

ityfora

ntibiotic

efficiency

(ii)Interferin

gwith

QS

commun

ication

Prom

otingdispersio

nand

degradation

Exam

ples

ofextractsor

compo

unds

(i)Gingere

xtract

(ii)U

rsolicacid

(i)Ca

sbaned

iterpene

(ii)C

oumaratee

ster

Cou

maratee

ster

(i)Soleno

psin

A(ii)N

aringenin

(iii)Fu

rano

neC-

30and-56

(iv)F

lavan-3-olC

atechin

(v)A

joene

(vi)Cou

maratee

ster

DNAs

eI1L2


Acknowledgment


References






































































































































































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology


ON

HO

O

ON

HO

O O

C4-HSL

3-Oxo-C12-HSL

(a) Native AHLs





NH

N

N

H

H H

O

O

NH

OnO

O

OO

NH H O

OO

Br

C9H19

(b) AHLs analogues



Manoalide

O

O O

OO

O

O

XH

OOH

OH

Br

OO

O

OH

HO























compo

unds

forP

aeruginosabiofi

lmform

ation

Naturalprod

uctscompo

unds

Orig

inClass

Activ

ities

References

QSinhibitio

nBiofi

lminhibitio

n(a)

Disp

ersio

nprom

otion

Synergywith

antib

iotic

Alginatelyase

Paeruginosa

Enzyme

minus+

++(1)

[134]

Ursolicacid

Diospyros

dend

oWelw

Triterpenoid

minus+(24h

)motility

NC

NC

[141]

p-Cou

maroyl-h

ydroxy-ursolicacid

Diospyros

dend

oWelw

Cou

maratee

stero

ftriterpene

NC

+(24h

)NC

NC

[142]

Zingeron

eZingiberoffi

cinaleR

osc

Phenoliccompo

und

NC

+(168

h)c-di-G

MP

NC

+(2)

[138139]

Casbaned

iterpene

Croton

nepetaefo

liusB

aill

Diterpenoid

NC

+(24h

)adherence

NC

NC

[140]

DNaseI

Bovine

pancreas

Enzyme

NC

+(18ndash24

h)+

+(3)

[137]

DNase-1L2

Hum

anstratum

corneum

[136]

Paraoxon

ases

1Hum

anandmurines

era

Enzyme(lacton

ase)

++(24h

)NC

NC

[116117]

Manoalid

eLu

ffarie

llavaria

bilis

(Polejaeff

1884)

(marineo

rganism

)Seste

rterpeno

id+(la

ssystem)

+(24h

)NC

NC

[113114]

Soleno

psin

ASolen

opsis

invicta(in

sectant)

Alkaloid

+(rhlsyste

m)

+(24h

)NC

NC

[115]

Catechin

Combretum

albiflorum

(Tul)Jong

kind

Flavon

oid

+(la

srhlsyste

ms)

+(24h

)NC

NC

[124]

Naringenin

Com

mercial

Flavon

oid

+(la

srhlsyste

ms)

+(48h

)NC

NC

[125]

Cou

maratee

ster

Dtrichocarpa

Baker

Phenoliccompo

und

+(la

srhlsyste

ms)

+(48h

)+

+(1)

[126]

Ajoene

Alliu

msativ

umL

Organosulfur

+(la

srhlsyste

ms)

+(96h

)NC

+(1)

[130]

Ellagica

cidderiv

atives

Term

inaliachebulaRe

tz

Phenoliccompo

und

+(la

srhlsyste

ms)

+(72h

)NC

+(1)

[120]

Rosm

arinicacid

Ocim

umbasilicu

mL

Phenoliccompo

und

+(la

srhlsyste

ms)

+(18h

)minus

NC

[89119

]

Eugeno

lSyzygium

arom

aticu

m(L)

MerrEt

Perry

Phenylprop

anoid

+(la

spqs

syste

ms)

+(24h

)NC

NC

[128]

Curcum

inCu

rcum

alongaL

Phenoliccompo

und

+(A

HLs)

+(48h

)NC

NC

[118]

Bergam

ottin

and


Citru

sparadisi

Macfad

(Rio

RedandMarsh

Whitegrapefruits)

Furocoum

arins

+(A

I-1and

AI-2)

+(24h

)NC

NC

[121]

Penicillica

cid

Penicilliu

mspecies

Furano

ne+(LasR

RhlR)

NC

NC

NC

[111]

Patulin

Furopyrano

ne+(LasRRh

lR)

mdashDagger

NC

+(1)

Emod

inRh

eum

palm

atum

LAnthraquino

ne+(docking

traR

)+(72h

)NC

+(3)

[123]

Baicalein

Scutellariabaica

lensis

Georgi

Flavon

oid

+(docking

traR

)+(72h

)NC

+(3)

[122]

+yesminusnoNC

notcom

mun

icated

DaggerPatulin

does

notaffectthed

evelo

pmento

fbiofilm

(a) Exp

erim

entd

uration

(1) A

minoglycosid

es(2)ciprofl

oxacin(3)am

picillin


Table2Synthetic

inhibitory

compo

unds

inPaeruginosa

biofi

lmform

ation

Synthetic

compo

unds

(Naturalcompo

undorigin)

Activ

ities

References

QSinhibitio

nBiofi

lminhibitio

n(a)

Disp

ersio

nprom

otion

Synergisticantib

iotic

andor

immun

edefense

effect

TAGEandCA

GE(Bromoageliferin)

NC

+(24h

)+

NC

[132]

Dihydrosventrin

(Sventrin

)NC

+(24h

)+

NC

[133]

N-(4-brom

o-ph

enylacetanoyl)-l-H

SL

N-(indo


(AHLs)

+AHLs

antagonist(la

ssystem)

+(24h

)NC

NC

[97]

3-oxo-C1

2-cyclo

hexano

ne(A

HLs)

+AHLs

antagonist(la

ssystem)

+(24h

)NC

NC

[98]

C10-cyclo

pentylam

ide(AHLs)

+(la

sIandrhlA)

+(24h

)NC

NC

[99]

Furano

neC-

30andC-

56(Furanon

e)+(la

srhlsystems)

+(24h

)[55100101]

S-ph


(Cysteinesulfoxide

alliin)

+(la

srhlsystems)

+(24h

)NC

NC

[148]

Diphenyld

isulfide

(Disu

lfide

deriv

atives

ofthea

lliinase

mediatedreactio

ns)

+lassystem

+(24h

)NC

NC

AzythromycinDagger

(Erythromycin)

+(gacA

lasa

ndrhlsystems)

+(72h

)+

+(1)

[103108109]

+yesminusnoNC

notcom

mun

icated

DaggerAt

subinh

ibito

ryconcentration

(a) Exp

erim

entd

uration

(1) A

minoglycosid

es


Curcumin Catechin

Bergamottin

Zingerone

Rosmarinic acid


Naringenin

Baicalein

Eugenol


HO

HO

HO

OHOH

OH

OHOH

OH

OH

OH

OH

OHO

OO

O

OO

O OHOH

OHOH

O

OR

O

HO

HOHO

HO

HO

HOHO

OH

OH

OH

O

O

O

O


O O O

O

O O

O

O

O O

O

OCH3

OCH3

OCH3 H3CO










Two-day old culture



(a) (b)






















Table3Factorsa

ffectingbiofi

lmlifestyleregu

latio

n

Biofi

lmlifestylecycle

StageI


StageII


StageIII

Maturation-1

(microcolony

developm

ent)

StageIV

Maturation-2

(maintenance)

StageV

Disp

ersio

n

Implicated

factors

c-di-G

MP

(i)Flagellaa

ndtype

IVpili

(ii)A

dhesins

(iii)PslPel


ication

lasI

(ii)T

ypeIVfim

briae

(iii)Matrix

compo

nentsPsl

PeleD

NA

(iv)L

ectin

AB

(v)rhlA


ication

(ii)M

atrix

compo

nentsPslPel

eDNA

(iii)rhlA

Rham

nolip

ids

Generaltarget

(i)Prom

otingplankton

iclifestyle

(ii)B

lockingsw

itchfro

mplankton

icto

biofi

lmlifestyle

Redu

cing

initialadhesio

nandinteraction

Interfe

ringwith

QS

commun

ication

(i)Re

activ

atingmetabolic

activ

ityfora

ntibiotic

efficiency

(ii)Interferin

gwith

QS

commun

ication

Prom

otingdispersio

nand

degradation

Exam

ples

ofextractsor

compo

unds

(i)Gingere

xtract

(ii)U

rsolicacid

(i)Ca

sbaned

iterpene

(ii)C

oumaratee

ster

Cou

maratee

ster

(i)Soleno

psin

A(ii)N

aringenin

(iii)Fu

rano

neC-

30and-56

(iv)F

lavan-3-olC

atechin

(v)A

joene

(vi)Cou

maratee

ster

DNAs

eI1L2


Acknowledgment


References






































































































































































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology


















compo

unds

forP

aeruginosabiofi

lmform

ation

Naturalprod

uctscompo

unds

Orig

inClass

Activ

ities

References

QSinhibitio

nBiofi

lminhibitio

n(a)

Disp

ersio

nprom

otion

Synergywith

antib

iotic

Alginatelyase

Paeruginosa

Enzyme

minus+

++(1)

[134]

Ursolicacid

Diospyros

dend

oWelw

Triterpenoid

minus+(24h

)motility

NC

NC

[141]

p-Cou

maroyl-h

ydroxy-ursolicacid

Diospyros

dend

oWelw

Cou

maratee

stero

ftriterpene

NC

+(24h

)NC

NC

[142]

Zingeron

eZingiberoffi

cinaleR

osc

Phenoliccompo

und

NC

+(168

h)c-di-G

MP

NC

+(2)

[138139]

Casbaned

iterpene

Croton

nepetaefo

liusB

aill

Diterpenoid

NC

+(24h

)adherence

NC

NC

[140]

DNaseI

Bovine

pancreas

Enzyme

NC

+(18ndash24

h)+

+(3)

[137]

DNase-1L2

Hum

anstratum

corneum

[136]

Paraoxon

ases

1Hum

anandmurines

era

Enzyme(lacton

ase)

++(24h

)NC

NC

[116117]

Manoalid

eLu

ffarie

llavaria

bilis

(Polejaeff

1884)

(marineo

rganism

)Seste

rterpeno

id+(la

ssystem)

+(24h

)NC

NC

[113114]

Soleno

psin

ASolen

opsis

invicta(in

sectant)

Alkaloid

+(rhlsyste

m)

+(24h

)NC

NC

[115]

Catechin

Combretum

albiflorum

(Tul)Jong

kind

Flavon

oid

+(la

srhlsyste

ms)

+(24h

)NC

NC

[124]

Naringenin

Com

mercial

Flavon

oid

+(la

srhlsyste

ms)

+(48h

)NC

NC

[125]

Cou

maratee

ster

Dtrichocarpa

Baker

Phenoliccompo

und

+(la

srhlsyste

ms)

+(48h

)+

+(1)

[126]

Ajoene

Alliu

msativ

umL

Organosulfur

+(la

srhlsyste

ms)

+(96h

)NC

+(1)

[130]

Ellagica

cidderiv

atives

Term

inaliachebulaRe

tz

Phenoliccompo

und

+(la

srhlsyste

ms)

+(72h

)NC

+(1)

[120]

Rosm

arinicacid

Ocim

umbasilicu

mL

Phenoliccompo

und

+(la

srhlsyste

ms)

+(18h

)minus

NC

[89119

]

Eugeno

lSyzygium

arom

aticu

m(L)

MerrEt

Perry

Phenylprop

anoid

+(la

spqs

syste

ms)

+(24h

)NC

NC

[128]

Curcum

inCu

rcum

alongaL

Phenoliccompo

und

+(A

HLs)

+(48h

)NC

NC

[118]

Bergam

ottin

and


Citru

sparadisi

Macfad

(Rio

RedandMarsh

Whitegrapefruits)

Furocoum

arins

+(A

I-1and

AI-2)

+(24h

)NC

NC

[121]

Penicillica

cid

Penicilliu

mspecies

Furano

ne+(LasR

RhlR)

NC

NC

NC

[111]

Patulin

Furopyrano

ne+(LasRRh

lR)

mdashDagger

NC

+(1)

Emod

inRh

eum

palm

atum

LAnthraquino

ne+(docking

traR

)+(72h

)NC

+(3)

[123]

Baicalein

Scutellariabaica

lensis

Georgi

Flavon

oid

+(docking

traR

)+(72h

)NC

+(3)

[122]

+yesminusnoNC

notcom

mun

icated

DaggerPatulin

does

notaffectthed

evelo

pmento

fbiofilm

(a) Exp

erim

entd

uration

(1) A

minoglycosid

es(2)ciprofl

oxacin(3)am

picillin


Table2Synthetic

inhibitory

compo

unds

inPaeruginosa

biofi

lmform

ation

Synthetic

compo

unds

(Naturalcompo

undorigin)

Activ

ities

References

QSinhibitio

nBiofi

lminhibitio

n(a)

Disp

ersio

nprom

otion

Synergisticantib

iotic

andor

immun

edefense

effect

TAGEandCA

GE(Bromoageliferin)

NC

+(24h

)+

NC

[132]

Dihydrosventrin

(Sventrin

)NC

+(24h

)+

NC

[133]

N-(4-brom

o-ph

enylacetanoyl)-l-H

SL

N-(indo


(AHLs)

+AHLs

antagonist(la

ssystem)

+(24h

)NC

NC

[97]

3-oxo-C1

2-cyclo

hexano

ne(A

HLs)

+AHLs

antagonist(la

ssystem)

+(24h

)NC

NC

[98]

C10-cyclo

pentylam

ide(AHLs)

+(la

sIandrhlA)

+(24h

)NC

NC

[99]

Furano

neC-

30andC-

56(Furanon

e)+(la

srhlsystems)

+(24h

)[55100101]

S-ph


(Cysteinesulfoxide

alliin)

+(la

srhlsystems)

+(24h

)NC

NC

[148]

Diphenyld

isulfide

(Disu

lfide

deriv

atives

ofthea

lliinase

mediatedreactio

ns)

+lassystem

+(24h

)NC

NC

AzythromycinDagger

(Erythromycin)

+(gacA

lasa

ndrhlsystems)

+(72h

)+

+(1)

[103108109]

+yesminusnoNC

notcom

mun

icated

DaggerAt

subinh

ibito

ryconcentration

(a) Exp

erim

entd

uration

(1) A

minoglycosid

es


Curcumin Catechin

Bergamottin

Zingerone

Rosmarinic acid


Naringenin

Baicalein

Eugenol


HO

HO

HO

OHOH

OH

OHOH

OH

OH

OH

OH

OHO

OO

O

OO

O OHOH

OHOH

O

OR

O

HO

HOHO

HO

HO

HOHO

OH

OH

OH

O

O

O

O


O O O

O

O O

O

O

O O

O

OCH3

OCH3

OCH3 H3CO










Two-day old culture



(a) (b)






















Table3Factorsa

ffectingbiofi

lmlifestyleregu

latio

n

Biofi

lmlifestylecycle

StageI


StageII


StageIII

Maturation-1

(microcolony

developm

ent)

StageIV

Maturation-2

(maintenance)

StageV

Disp

ersio

n

Implicated

factors

c-di-G

MP

(i)Flagellaa

ndtype

IVpili

(ii)A

dhesins

(iii)PslPel


ication

lasI

(ii)T

ypeIVfim

briae

(iii)Matrix

compo

nentsPsl

PeleD

NA

(iv)L

ectin

AB

(v)rhlA


ication

(ii)M

atrix

compo

nentsPslPel

eDNA

(iii)rhlA

Rham

nolip

ids

Generaltarget

(i)Prom

otingplankton

iclifestyle

(ii)B

lockingsw

itchfro

mplankton

icto

biofi

lmlifestyle

Redu

cing

initialadhesio

nandinteraction

Interfe

ringwith

QS

commun

ication

(i)Re

activ

atingmetabolic

activ

ityfora

ntibiotic

efficiency

(ii)Interferin

gwith

QS

commun

ication

Prom

otingdispersio

nand

degradation

Exam

ples

ofextractsor

compo

unds

(i)Gingere

xtract

(ii)U

rsolicacid

(i)Ca

sbaned

iterpene

(ii)C

oumaratee

ster

Cou

maratee

ster

(i)Soleno

psin

A(ii)N

aringenin

(iii)Fu

rano

neC-

30and-56

(iv)F

lavan-3-olC

atechin

(v)A

joene

(vi)Cou

maratee

ster

DNAs

eI1L2


Acknowledgment


References






































































































































































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology


Table2Synthetic

inhibitory

compo

unds

inPaeruginosa

biofi

lmform

ation

Synthetic

compo

unds

(Naturalcompo

undorigin)

Activ

ities

References

QSinhibitio

nBiofi

lminhibitio

n(a)

Disp

ersio

nprom

otion

Synergisticantib

iotic

andor

immun

edefense

effect

TAGEandCA

GE(Bromoageliferin)

NC

+(24h

)+

NC

[132]

Dihydrosventrin

(Sventrin

)NC

+(24h

)+

NC

[133]

N-(4-brom

o-ph

enylacetanoyl)-l-H

SL

N-(indo


(AHLs)

+AHLs

antagonist(la

ssystem)

+(24h

)NC

NC

[97]

3-oxo-C1

2-cyclo

hexano

ne(A

HLs)

+AHLs

antagonist(la

ssystem)

+(24h

)NC

NC

[98]

C10-cyclo

pentylam

ide(AHLs)

+(la

sIandrhlA)

+(24h

)NC

NC

[99]

Furano

neC-

30andC-

56(Furanon

e)+(la

srhlsystems)

+(24h

)[55100101]

S-ph


(Cysteinesulfoxide

alliin)

+(la

srhlsystems)

+(24h

)NC

NC

[148]

Diphenyld

isulfide

(Disu

lfide

deriv

atives

ofthea

lliinase

mediatedreactio

ns)

+lassystem

+(24h

)NC

NC

AzythromycinDagger

(Erythromycin)

+(gacA

lasa

ndrhlsystems)

+(72h

)+

+(1)

[103108109]

+yesminusnoNC

notcom

mun

icated

DaggerAt

subinh

ibito

ryconcentration

(a) Exp

erim

entd

uration

(1) A

minoglycosid

es


Curcumin Catechin

Bergamottin

Zingerone

Rosmarinic acid


Naringenin

Baicalein

Eugenol


HO

HO

HO

OHOH

OH

OHOH

OH

OH

OH

OH

OHO

OO

O

OO

O OHOH

OHOH

O

OR

O

HO

HOHO

HO

HO

HOHO

OH

OH

OH

O

O

O

O


O O O

O

O O

O

O

O O

O

OCH3

OCH3

OCH3 H3CO










Two-day old culture



(a) (b)






















Table3Factorsa

ffectingbiofi

lmlifestyleregu

latio

n

Biofi

lmlifestylecycle

StageI


StageII


StageIII

Maturation-1

(microcolony

developm

ent)

StageIV

Maturation-2

(maintenance)

StageV

Disp

ersio

n

Implicated

factors

c-di-G

MP

(i)Flagellaa

ndtype

IVpili

(ii)A

dhesins

(iii)PslPel


ication

lasI

(ii)T

ypeIVfim

briae

(iii)Matrix

compo

nentsPsl

PeleD

NA

(iv)L

ectin

AB

(v)rhlA


ication

(ii)M

atrix

compo

nentsPslPel

eDNA

(iii)rhlA

Rham

nolip

ids

Generaltarget

(i)Prom

otingplankton

iclifestyle

(ii)B

lockingsw

itchfro

mplankton

icto

biofi

lmlifestyle

Redu

cing

initialadhesio

nandinteraction

Interfe

ringwith

QS

commun

ication

(i)Re

activ

atingmetabolic

activ

ityfora

ntibiotic

efficiency

(ii)Interferin

gwith

QS

commun

ication

Prom

otingdispersio

nand

degradation

Exam

ples

ofextractsor

compo

unds

(i)Gingere

xtract

(ii)U

rsolicacid

(i)Ca

sbaned

iterpene

(ii)C

oumaratee

ster

Cou

maratee

ster

(i)Soleno

psin

A(ii)N

aringenin

(iii)Fu

rano

neC-

30and-56

(iv)F

lavan-3-olC

atechin

(v)A

joene

(vi)Cou

maratee

ster

DNAs

eI1L2


Acknowledgment


References






































































































































































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology


Curcumin Catechin

Bergamottin

Zingerone

Rosmarinic acid


Naringenin

Baicalein

Eugenol


HO

HO

HO

OHOH

OH

OHOH

OH

OH

OH

OH

OHO

OO

O

OO

O OHOH

OHOH

O

OR

O

HO

HOHO

HO

HO

HOHO

OH

OH

OH

O

O

O

O


O O O

O

O O

O

O

O O

O

OCH3

OCH3

OCH3 H3CO










Two-day old culture



(a) (b)






















Table3Factorsa

ffectingbiofi

lmlifestyleregu

latio

n

Biofi

lmlifestylecycle

StageI


StageII


StageIII

Maturation-1

(microcolony

developm

ent)

StageIV

Maturation-2

(maintenance)

StageV

Disp

ersio

n

Implicated

factors

c-di-G

MP

(i)Flagellaa

ndtype

IVpili

(ii)A

dhesins

(iii)PslPel


ication

lasI

(ii)T

ypeIVfim

briae

(iii)Matrix

compo

nentsPsl

PeleD

NA

(iv)L

ectin

AB

(v)rhlA


ication

(ii)M

atrix

compo

nentsPslPel

eDNA

(iii)rhlA

Rham

nolip

ids

Generaltarget

(i)Prom

otingplankton

iclifestyle

(ii)B

lockingsw

itchfro

mplankton

icto

biofi

lmlifestyle

Redu

cing

initialadhesio

nandinteraction

Interfe

ringwith

QS

commun

ication

(i)Re

activ

atingmetabolic

activ

ityfora

ntibiotic

efficiency

(ii)Interferin

gwith

QS

commun

ication

Prom

otingdispersio

nand

degradation

Exam

ples

ofextractsor

compo

unds

(i)Gingere

xtract

(ii)U

rsolicacid

(i)Ca

sbaned

iterpene

(ii)C

oumaratee

ster

Cou

maratee

ster

(i)Soleno

psin

A(ii)N

aringenin

(iii)Fu

rano

neC-

30and-56

(iv)F

lavan-3-olC

atechin

(v)A

joene

(vi)Cou

maratee

ster

DNAs

eI1L2


Acknowledgment


References






































































































































































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology


Two-day old culture



(a) (b)






















Table3Factorsa

ffectingbiofi

lmlifestyleregu

latio

n

Biofi

lmlifestylecycle

StageI


StageII


StageIII

Maturation-1

(microcolony

developm

ent)

StageIV

Maturation-2

(maintenance)

StageV

Disp

ersio

n

Implicated

factors

c-di-G

MP

(i)Flagellaa

ndtype

IVpili

(ii)A

dhesins

(iii)PslPel


ication

lasI

(ii)T

ypeIVfim

briae

(iii)Matrix

compo

nentsPsl

PeleD

NA

(iv)L

ectin

AB

(v)rhlA


ication

(ii)M

atrix

compo

nentsPslPel

eDNA

(iii)rhlA

Rham

nolip

ids

Generaltarget

(i)Prom

otingplankton

iclifestyle

(ii)B

lockingsw

itchfro

mplankton

icto

biofi

lmlifestyle

Redu

cing

initialadhesio

nandinteraction

Interfe

ringwith

QS

commun

ication

(i)Re

activ

atingmetabolic

activ

ityfora

ntibiotic

efficiency

(ii)Interferin

gwith

QS

commun

ication

Prom

otingdispersio

nand

degradation

Exam

ples

ofextractsor

compo

unds

(i)Gingere

xtract

(ii)U

rsolicacid

(i)Ca

sbaned

iterpene

(ii)C

oumaratee

ster

Cou

maratee

ster

(i)Soleno

psin

A(ii)N

aringenin

(iii)Fu

rano

neC-

30and-56

(iv)F

lavan-3-olC

atechin

(v)A

joene

(vi)Cou

maratee

ster

DNAs

eI1L2


Acknowledgment


References






































































































































































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology












Table3Factorsa

ffectingbiofi

lmlifestyleregu

latio

n

Biofi

lmlifestylecycle

StageI


StageII


StageIII

Maturation-1

(microcolony

developm

ent)

StageIV

Maturation-2

(maintenance)

StageV

Disp

ersio

n

Implicated

factors

c-di-G

MP

(i)Flagellaa

ndtype

IVpili

(ii)A

dhesins

(iii)PslPel


ication

lasI

(ii)T

ypeIVfim

briae

(iii)Matrix

compo

nentsPsl

PeleD

NA

(iv)L

ectin

AB

(v)rhlA


ication

(ii)M

atrix

compo

nentsPslPel

eDNA

(iii)rhlA

Rham

nolip

ids

Generaltarget

(i)Prom

otingplankton

iclifestyle

(ii)B

lockingsw

itchfro

mplankton

icto

biofi

lmlifestyle

Redu

cing

initialadhesio

nandinteraction

Interfe

ringwith

QS

commun

ication

(i)Re

activ

atingmetabolic

activ

ityfora

ntibiotic

efficiency

(ii)Interferin

gwith

QS

commun

ication

Prom

otingdispersio

nand

degradation

Exam

ples

ofextractsor

compo

unds

(i)Gingere

xtract

(ii)U

rsolicacid

(i)Ca

sbaned

iterpene

(ii)C

oumaratee

ster

Cou

maratee

ster

(i)Soleno

psin

A(ii)N

aringenin

(iii)Fu

rano

neC-

30and-56

(iv)F

lavan-3-olC

atechin

(v)A

joene

(vi)Cou

maratee

ster

DNAs

eI1L2


Acknowledgment


References






































































































































































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology


Acknowledgment


References






































































































































































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

































































































































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

review article the formation of biofilms by pseudomonas...

Documents