the v. fischeri autoinducer n-( -ketocaproyl)- l -homoserine lactone

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Page 1: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone
Page 2: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone
Page 3: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

The V. fischeri Autoinducer

N-(-ketocaproyl)-L-homoserine lactone

Page 4: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

LuxR

target gene

LuxI LuxR

Quorum Sensing

Page 5: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

Acyl-Homoserine Lactone Autoinducers

Page 6: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

LuxI-LuxR Quorum Sensing Systems

V. fischeri

P.aeruginosa

A. tumefaciens

E. carotovora

Density dependent luminescence

Virulence factors

Conjugal transfer of Ti plasmid

Antibiotic synthesis

Page 7: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

LuxN

LuxQ

H

LuxU

H D

DH

D HTH

LuxO

AI-1

AI-2

Quorum Sensing in V. harveyi

LuxCDABELuxR

LuxP

Page 8: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

Quorum Sensing in E. coli and Salmonella

Page 9: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

Klebsiella pneumoniae

Lactococcus lactis

Leuconostoc oenos

Listeria monocytogenes

Neisseria gonorrhoeae

Neisseria meningitidis

Pasteurella multocida

Porphyromonas gingivalis

Proteus mirabilis

Salmonella paratyphi

Salmonella typhi

Salmonella typhimurium

Bacillus anthracis

Bacillus halodurans

Bacillus subtilis

Borrelia burgdorferi

Campylobacter jejuni

Clostridium acetobolyticum

Clostridium difficile

Clostridium perfringens

Deinococcus radiodurans

Escherichia coli

Enterococcus faecalis

Haemophilus influenzae

Helicobacter pylori

Shewanella putrefaciens

Staphylococcus aureus

Staphylococcus epidermidis

Streptococcus gordonii

Streptococcus mutans

Streptococcus pneumoniae

Streptococcus pyogenes

Vibrio anguillarum

Vibrio cholerae

Vibrio harveyi

Vibrio vulnificus

Yersinia pestis

Bacteria That Contain luxS

Page 10: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

luxS

pfs

metK

Page 11: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone
Page 12: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

MetK

Pfs

Pfs

Page 544

Page 13: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

Met

SAM

SAH MTA

SRH MTR

4,5-Dihydroxy-2,3-pentanedione + HC

?

MetK

Pfs Pfs

SAM Utilization

Page 14: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

Met

SAM

SAH MTA

SRH MTR

4,5-Dihydroxy-2,3-pentanedione + HC

?

MetK

Pfs Pfs

SAM Utilization

LuxS?

Page 15: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

Met

SAM

SAH MTA

SRH MTR

AI-2 + HC ?

MetK

Pfs Pfs

SAM Utilization

LuxS

Page 16: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

SRH 4,5-Dihydroxy-2,3-pentanedione

Homocysteine+

The LuxS Reaction

Page 17: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

AI-2 Could be a Furanone

MHF DMHF HF DHCP

Page 18: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

LuxN

LuxQ

H

LuxU

H D

DH

D HTH

LuxO

AI-1

AI-2

Quorum Sensing in V. harveyi

LuxCDABELuxR

LuxP

Page 19: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

Holo-LuxP

Page 20: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone
Page 21: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone
Page 22: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone
Page 23: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

Boron is ubiquitous in the biosphere

Boron is required by a number of organisms, but for poorly characterized reasons

Sea water 0.4 mM (primarily boric acid)L.A. tap water 40 μMSoils 2-100 ppmMarine plants 120 ppmLand plants 50 ppmMarine animals 20-50 ppmLand animals 0.5 ppm

Vascular plants cell wall? pollination?DiatomsCyanobacteria heterocyst formationZebrafish embryogenesis

Page 24: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

11B NMR

holo-LuxP

filtered

apo-LuxP

Page 25: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

Synthesis of AI-2

Page 26: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

Boric Acid Induces Lux in V. harveyi

Page 27: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

Synthesis of AI-2

Page 28: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

Targets of AI-2Vibrio harveyi Bioluminescence, Biofilms

Vibrio cholerae Virulence, Biofilms

Salmonella typhimurium ABC transporter

Salmonella typhi Biofilms

Escherichia coli O157:H7 Type III Secretion (virulence)

Porphyromonas gingivalis Hemin acquisition genes, virulence factors

Shigella flexneri VirB (virulence factor)

Streptococcus pyogenes Secreted protease

Actinobacillus actinomycetemcomitans Periodontal virulence, Mixed-species

biofilms

Photorhabdus luminescens Antibiotic production

Neisseria meningitidis Virulence/bacteremia

Borrelia burgdorferi Virulence

Clostridium perfringens Virulence

Campylobacter jejuni Motility

MicroarraysEscherichia coli K12 ~300 genes Escherichia coli O157:H7 ~400 genesVibrio cholerae El Tor ~70 genes (virulence regulon)

Page 29: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

LuxILuxLM

AI-1

Met

SAM

SAH MTA

SRH MTR

AI-2 + HC ?

MetK

Pfs Pfs

LuxS

Biosynthesis of AI-1 and AI-2

Page 30: The V. fischeri Autoinducer N-(  -ketocaproyl)- L -homoserine lactone

LuxN

LuxQ

H

LuxU

H D

DH

D HTH

LuxO

AI-1

AI-2

Quorum Sensing in V. harveyi

LuxCDABELuxR

LuxP