Mechanisms of resistance: bacteria destroy antibiotics · antibiotics, is normal for a particular bacterial genus, species or entire bacterial group. It may be the result of the lack

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

Woodford et al. Antimicrob Agents Chemother 2009; 53: 4472-82

Neatpackagesofmulti-resistance

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