Mechanisms of resistance: The many ways in which
bacteria destroy antibiotics
Dr Rossana RosaInfectiousDiseasesconsultant,UnityPointHealth,DesMoines,
Iowa,USA
Therearetwotypesofresistance:IntrinsicorInherentandAcquired
IntrinsicorInherent:
Thisiswhenresistancetoaparticularantibiotic,orgroupofantibiotics,isnormalforaparticularbacterialgenus,speciesorentirebacterialgroup.Itmaybetheresultofthelackofatargetfortheparticularantibiotic,orbecausethatdrugcan'tgettoitstarget.
- Exampleswouldbevancomycinorlinezolidresistanceingram-negatives.They'reresistanttovancomycinbecausethemoleculecan'tgetthroughthegram-negativeoutermembrane.Linezolidisinactivebecauseit'spumpedoutofgram-negativecells.
Acquired:
Thisisthetypeofresistancewheremostisolatesofabacterialspecies,genus,orgroup,wouldbefullysusceptibletotheparticularantibiotic,butwhereresistancemayariseinafew,orinsomecasesinmanyisolates.Itmayarisethroughmutationofachromosomalgene.
- Enterobacteriaceae oftendevelopresistancebyacquiringnewDNA.Thisisanexampleofso-calledhorizontalgenetransfer,horizontalspread.ThetypicalvehicleresponsibleforthiswouldbearingofDNAknownasaplasmid.
ThisvideoisusedbykindpermissionoftheUniversityofDundee.FutureLearncourse- AntimicrobialStewardship:Managingantibioticresistance.
Bacteria don’t keep resistance to themselves
Permission to use cartoon by Nick D. Kimhttp://www.hollver.is/mat/hrammi/matsjuk/Image4.gif
Neatpackagesofmulti-resistanceAntibiotic classes Genes Mechanism
Aminoglycosidesaac6’-Ib-cr
aadA5Modify drug
β-lactams
blaCTX-M-15
blaOXA-1
blaTEM-1
Destroy drug
Chloramphenicol catB4 Modify drug
Macrolides mph(A) Efflux
Fluoroquinolones aac6’-Ib-cr Modify drug
Sulfonamides sulI By-passTrimethoprim dhfrXVII By-passTetracycline tet(A) Efflux
TheForensicsofAMR
• Resistance involves– emergence of
mutations– spread of
resistance genes– spread of resistant
strains
• Tracking and characterizing – the resistant strains– their resistance
genes
Genes
Gene carriers
IS, In, Tn, plasmids
Host species
Strains, clones, phylogenetic groups, virulence traits, co-resistance
Patients
Hospital / community setting; risk factors