Table 1

Mechanisms of antimicrobial resistance and virulence

Antimicrobial groupMechanism of resistanceImplication in virulencePathogen(s)Reference(s)
β–LactamsPBP modifications
    Penicillin–binding protein 2 (mecA)Regulation of Agr quorum–sensing system; biofilm formation; attenuated virulence in mouse model; infection persistence S. aureus 15
    SCCmecExpression of phenol-soluble modulins S. aureus 17
    PBP2b-PBPXAttenuated virulence in mouse model S. pneumoniae 19
    PBP7-8Attenuated virulence in mouse model A. baumannii 25
β-Lactamases
    CTX-M-type ESBLsUsually plasmid borne; increased virulence not clearly demonstrated E. coli 31, 32
    OXA-10-like, OXA24, and SFO-1Fitness cost in common host (changes in peptidoglycan composition) E. coli 34
    AmpCFitness cost S. enterica 35
    AmpC/AmpD/AmpRFitness cost and virulence; AmpR (transcriptional regulator of ampC) also controls expression of alginate production and quorum-sensing system; type 3 fimbrial gene expression and biofilm formation P. aeruginosa, K. pneumoniae 10, 37, 38
    β-Lactamases (ESBL)Invasion of epithelial cells; plasmid-carried genes K. pneumoniae 36
    IMP typesNo significant impact in virulence in animal model P. aeruginosa 33
    PER-1Adhesion cell (mechanism not known) A. baumannii 41
Porins
    OmpAAdhesion cell; induction of cell death; biofilm formation A. baumannii 49, 56
    Omp33-36Cell adhesion; induction of cell death; biofilm formation A. baumannii 49, 56
    CarOAttenuated virulence in mouse model; biofilm formation A. baumannii 55
    OprD-like a Attenuated virulence in mouse model A. baumannii 55
    OmpCAdhesion, cell invasion, and intestinal colonization (Crohn's disease) E. coli 58
    OmpFAdhesion to Hep-2 cells E. coli 60
    OmpK35-K36Resistance to phagocytosis; metabolic fitness cost K. pneumoniae 9
Efflux pumps
    AdeABCColonization, infection, and persistence of microorganism in host A. baumannii 148, 149, 437
    AcrAB-TolCColonization, infection, and persistence of microorganism in host Enterobacteriaceae 68
    Mex systemColonization, persistence, and expression of virulence genes; MexAB is involved in quorum-sensing/quorum-quenching system; MexCD is associated with regulation of type III secretion system; MexEF regulation implicated in GacA/RsmA/RsmB (RsmZ) signal transduction system P. aeruginosa 66, 94, 95, 96, 102
    SecDFExpression of virulence genes E. coli, B. subtilis, S. aureus 103
AminoglycosidesEfflux pumps (as for β-lactams above)
Ribosomal methylases/RmtCNo fitness cost E. coli 104
Ribosomal mutations/RpsLFitness cost E. coli, Salmonella spp., M. tuberculosis 13, 111 115
FluoroquinolonesTarget modifications (topoisomerases and DNA gyrases)No fitness cost; presence of the type III secretion system genes P. aeruginosa 119
Fitness cost S. enterica 120
Higher risk of invasive illness or death S. Typhimurium 123
Virulence gene expression and cell viability S. flexneri 124
No fitness cost E. coli 125
Fitness cost A. baumannii 121
Inactivation of the sarA regulator gene S. aureus 129
Decreased colonization S. pneumoniae 132
Efflux pumps
    Multidrug resistance efflux transporters (NorA, NorB, NorC, Tet38, and AbcA)Global transcriptional regulator (MgrA) S. aureus 133
    AcrAB-TolC (as for β-lactams)
    Mex system (as for β-lactams)
    BepDE systemContribution to virulence (unknown mechanism) B. suis 134
QnrFitness cost E. coli 138
Porins (as for β-lactams)
Tetracyclines and tigecyclinesEfflux pumps
    tet genes such as Tet(A) or Tet(B)Increased expression of virulence genes but decreased fitness E. coli 140
    AdeABC (as for β-lactams)
    AcrAB (as for β-lactams)
Ribosomal protection
    tet44 Associated with type IV secretion system C. fetus 142
    Mutations in 16S rRNARibosomal mutations and others increase antibiotic resistance but with deleterious effects on fitness H. pylori 143
Antibiotic modification
    tetX geneNo fitness cost in B. fragilis; probable fitness cost in aerobic Gram-negative bacteria B. fragilis 144, 145
MacrolidesEfflux pumps
    MuxABC-OmpDecreased twitching motility P. aeruginosa 151
    BpEAB-OprBExcretion of acyl homoserine lactone quorum-sensing molecules (biofilms, siderophores, and phospholipase C) B. pseudomallei 153
    MtrC-MtrD-MtrEFitness cost N. gonorrhoeae 154
Ribosomal methylation
    erm class genesPresence of virulence genes (gelE) E. faecalis 155
    23S rRNA mutationFitness cost C. jejuni 156, 157
GlycopeptidesCell wall modifications
    GISAFitness cost S. aureus 130, 161
Attenuated virulence in nonmammalian model system G. mellonella S. aureus 162
Modified peptidoglycan target
    VanA and VanB phenotypesFitness cost Enterococcus spp 165
Oxazilidones (linezolid)rRNA mutationsFitness costCoagulase-negative staphylococci, S. aureus, S. pneumoniae 170, 171
rRNA methylationFitness cost S. aureus 173, 174
Colistin, polymyxin BLipopolysaccharide modifications
    PmrA-PmrBGlobal regulation, including virulence and resistance S. enterica 175
    SurA, TolB, and GndIncreased virulence in mouse model S. enterica 177
    PhoP-PhoQGlobal regulation, including virulence and resistance S. enterica, P. aeruginosa 197, 439
    LpxA, LpxD, or LpxC b Fitness cost by restructuring of the bacterial surface A. baumannii 190, 191
    PmrC-PmrA-PmrB b Fitness cost in in vitro experiments and decreased virulence in mouse model A. baumannii 188, 193, 194
    PsrARegulation of virulence and resistance (adaptation to swarming motility) P. aeruginosa 195
Efflux pumps
    YejABEFIncreased virulence in mouse model of gastric infections; involved in proliferation capacity inside macrophages and epithelial cells S. enterica 198
Increased production of nonessential antimicrobial target
    Overproduction of OMVsIncreased virulence, carrying virulence factors such as toxins E. coli 199
    Overproduction of bacterial capsuleIncreased virulence, evasion of phagocytosis, and complement resistance K. pneumoniae, S. pneumoniae, P. aeruginosa 200, 201
  • a Implication in resistance not clearly demonstrated.

  • b Implication in virulence not clearly demonstrated.