TABLE 1.
Gene name | Product | Alteration(s) or mutation(s) [number of isolates harboring the mutation] | References | Antibiotics affecteda |
gyrA | DNA gyrase subunit A | T83I [9], G663C [1], V671I [6], S859C [1], G860S [6], D893E [6], A900G [6], and S903A [6] | *Subedi et al., 2018; Do Nascimento et al., 2020; Papagiannitsis et al., 2020 | FQ |
gyrB | DNA gyrase subunit B | wt | FQ | |
parE | DNA topoisomerase IV subunit B | E533D [8] | *Dunham et al., 2010 | FQ |
parC | DNA topoisomerase IV subunit A | S87L [9], S197L [1], and P572T [3] | *Subedi et al., 2018; Do Nascimento et al., 2020 | FQ |
rpoB | DNA-directed RNA polymerase beta chain | V51I [14] | Do Nascimento et al., 2020 | RIF |
pmrA | Two-component regulator system response regulator PmrA | L71R [11] | Snesrud et al., 2018; Do Nascimento et al., 2020 | COL |
pmrB | Two-component regulator system signal sensor kinase PmrB | S2P [10], A4T [10], V6A [6], V15I [10], G68S [10], and Y345H [14] | Snesrud et al., 2018; Do Nascimento et al., 2020 | COL |
parS | Two-component sensor | R7H [2], L137P [6], S277N [1], and H398R [16] | *López-Causapé et al., 2018a | COL, IMI, MER, CEF, AMG, FQ |
parR | Two-component sensor | R70W [3], L153R [7], and S170N [7] | *Olsson et al., 2020 | COL, IMI, MER, CEF, AMG, FQ |
mexX | Resistance-nodulation-cell division (RND) multidrug efflux membrane fusion protein MexX precursor | A30T [4], V309I [1], K329Q [14], L331V [14], and W358R [14] | Vettoretti et al., 2009; Olsson et al., 2020 | CEF, AMG, FQ |
mexY | RND multidrug efflux transporter MexY | A501V [15], S530G [6], I536V [10]T543A [8], G589A [11], Q840E [10], N1036T [10], and Q1039R [12] | Vettoretti et al., 2009; Olsson et al., 2020 | |
mexZ | Transcriptional regulator of the mexXY multidrug transporter operon | D83E [1], G89S [2], and L138R [2] | *López-Causapé et al., 2018b | |
mexC | RND multidrug efflux membrane fusion protein MexC precursor | R43Q [1], T142A [1], E218Q [3], A229E [3], A244T [3], H277R [6], S2806 [1], S297A [14], E314K [1], A345T [4], P350S [6], and A351V [4] | IMI, MER, FQ | |
mexD | RND multidrug efflux transporter MexD | T87S [4], A155T [1], E257Q [7], T286M [1], V434A [1], F597Y [1], V660I [1], N669D [1], S685G [1], I703V [1], S845A [14], S915A [1], I982V [1], K1031R [3], and S1040T [1] | Papp-Wallace et al., 2019 | |
oprJ | Multidrug efflux outer membrane protein OprJ precursor | D68G [2], M69V [8], A211V [1], A260V [1], Q267R [6], and T376S [1] | Papp-Wallace et al., 2019; Olsson et al., 2020 | |
nfxB | Transcriptional regulator NfxB | R21H [1], D56G [1] | *Monti et al., 2013 | |
mexT | Transcriptional regulator MexT | F94I [1] | *Neves et al., 2019 | IMI, MER, FQ |
mexE | RND multidrug efflux membrane fusion protein MexE precursor | S8F [3], A80G [1], A231T [1], D353F [2], and D370E [2] | Olsson et al., 2020 | |
mexF | RND multidrug efflux transporter MexF | D230A [2], D667E [1], and A843T [1] | ||
oprN | Multidrug efflux outer membrane protein OprN precursor | A4T [1], S13P [7], and A410S [2] | Olsson et al., 2020 | |
mexA | RND multidrug efflux membrane fusion protein MexA precursor | K76Q [1] | IMI, MER, CEF, AMG, FQ | |
mexB | RND multidrug efflux transporter MexB | I186V [1], G957D [2], S1041E [4], and V1042A [4] | Neves et al., 2019; Olsson et al., 2020 | |
oprM | Major intrinsic multiple antibiotic resistance efflux outer membrane protein OprM precursor | D448N [1] | Olsson et al., 2020 | |
mexR | Multidrug resistance operon repressor MexR | V126E [13] | *Olsson et al., 2020 | |
nalC | Transcriptional regulator NalC | G71E [14], D79E [3], A145V [2], and S209R [7] | Horna et al., 2018, 2019 | |
nalD | Transcriptional regulator NalD | W205R [1] | ||
oprD | Basic amino acid, basic peptide and imipenem outer membrane porin OprD precursor | D43N [1], S57E [4], S59R [4], T103S [3], K115T [4], V127L [9], F170L [4], E185Q [13], P186G [13], V189T [13], E202Q [10], I210A [10], E230K [10], S240T [10], N262T [10], A267S [1], T276A [9], A281G [9], K296Q [9], Q301E [9], R310E [1], G312R [6], A315G [11], L347M [8], M372V [9], N375S [9], N376S [9], V377S [9], G378S [9], K380A [9], N381G [9], Y382L [9], T3939 [6], N394T [6], L395W [6], Y399P [6], V400S [6], V401T [6], Q402S [6], S403A [3], | Díaz-Ríos et al., 2021; Horna et al., 2018 | IMI, MER |
G404R [6], K407R [6], D408P [6], L409R [6], S410T [6], F411C [6], Q424E [3], and G425A [3] | ||||
F308_S349del [1], S373del [9], G383del [9], E396Edel [6], A397del [6], I414_L443 del [6], and W277_L443del[2] | ||||
ampC | Beta-lactamase precursor | P7S [3], F19L [1], G27D [5],R79Q [1], T105A [14], Q155R [1], L200F [1]V205L [7], V356I [5], and G391A [7] | *Cabot et al., 2012; Subedi et al., 2018 | C/T, CAZ/AVI |
ampD | Beta-lactamase expression regulator AmpD | A29V [1], Q44H [1], E68D [1], G148A [9], and S175L [1] | Cabot et al., 2012; Do Nascimento et al., 2020 | CAZ, CEF, PPT |
ampDh2 | Beta-lactamase expression regulator AmpDh2 | V40I [2], V89D [1] | ||
ampDh3 | Beta-lactamase expression regulator AmpDh3 | I67T [1], A208V [1], and A219T [6] | Díaz-Ríos et al., 2021 | |
ampR | Transcriptional regulator AmpR | E114A [2], S179T [1], A194S [1], I251V [1], G283E [13], E287G [7], M288R [6], M288Q [7], A290V [7], V291L [7], and A293S [7] | Cabot et al., 2012; Subedi et al., 2018 |
Those mutations/polymorphisms that are previously described are underlined. del(deletion). *Mutations previously detected associated with increased antimicrobial resistance.
aFQs, fluoroquinolone; RIF, rifampicin; COL, colistin; IMI, imipenem; MER, meropenem; CEF, cefepime; AMGs, AMGnoglycosides; CAZ/AVI, ceftazidime/avibactam; C/T, ceftolozane/tazobactam; PPT, piperacillin-tazobactam.