Table 1.
Main genes and mutations known to be involved in increased P. aeruginosa antibiotic resistance.
| Gene | Resistance mechanisms/altered target | Antibiotics affecteda | Type of mutation | Relevant examples of gain-of-function mutations | Reference |
|---|---|---|---|---|---|
| gyrA | DNA gyrase | FQ | Gain-of-function | G81D, T83A, T83I, Y86N, D87G, D87N, D87Y, Q106L | Bruchmann et al., 2013; Kos et al., 2015; Cabot et al., 2016b; Del Barrio-Tofiño et al., 2017; López-Causapé et al., 2017 |
| gyrB | DNA gyrase | FQ | Gain-of-function | S466F, S466Y, Q467R, E468D | Bruchmann et al., 2013; Kos et al., 2015; Del Barrio-Tofiño et al., 2017; López-Causapé et al., 2017 |
| parC | DNA topoisomerase IV | FQ | Gain-of-function | S87L, S87W | Bruchmann et al., 2013; Kos et al., 2015; Cabot et al., 2016b; Del Barrio-Tofiño et al., 2017 |
| parE | DNA topoisomerase IV | FQ | Gain-of-function | S457G, S457T, E459D, E459K | Bruchmann et al., 2013; Kos et al., 2015; Del Barrio-Tofiño et al., 2017; López-Causapé et al., 2017 |
| pmrA | Lipopolysaccharide (lipid A) | COL | Gain-of-function | L157Q | Lee and Ko, 2014 |
| pmrB | Lipopolysaccharide (lipid A) | COL | Gain-of-function | L14P, A54V, R79H, R135Q, A247T, A248T, A248V, R259H, M292I, M292T | Barrow and Kwon, 2009; Moskowitz et al., 2012 |
| phoQ | Lipopolysaccharide (lipid A) | COL | Loss-of-function | ||
| parR | Lipopolysaccharide (lipid A) | COL | Gain-of-function | M59I, E156K | Muller et al., 2011; Guénard et al., 2014 |
| OprD downregulation | IMP, MER | ||||
| MexEF-OprN hyperproduction | FQ | ||||
| MexXY-OprM hyperproduction | FQ, AMG, CEF | ||||
| parS | Lipopolysaccharide (lipid A) | COL | Gain-of-function | L14Q, V101M, L137P, A138T, A168V Q232E, G361R | Muller et al., 2011; Fournier et al., 2013; Guénard et al., 2014 |
| OprD downregulation | IMP, MER | ||||
| MexEF-OprN hyperproduction | FQ | ||||
| MexXY-OprM hyperproduction | FQ, AMG, CEF | ||||
| cprS | Lipopolysaccharide (lipid A) | COL | Gain-of-function | R241C | Gutu et al., 2013 |
| colR | Lipopolysaccharide (lipid A) | COL | Gain-of-function | D32N | Gutu et al., 2013 |
| colS | Lipopolysaccharide (lipid A) | COL | Gain-of-function | A106V | Gutu et al., 2013 |
| mexR | MexAB-OprM hyperproduction | FQ, CAZ, CEF, PPT, MER, CAZ/AVI | Loss-of-function | ||
| nalC | MexAB-OprM hyperproduction | FQ, CAZ, CEF, PPT, MER, CAZ/AVI | Loss-of-function | ||
| nalD | MexAB-OprM hyperproduction | FQ, CAZ, CEF, PPT, MER, CAZ/AVI | Loss-of-function | ||
| nfxB | MexCD-OprJ hyperproduction | FQ, CEF | Loss-of-function | ||
| mexS | MexEF-OprN hyperproduction | FQ | Loss-of-function | ||
| OprD downregulation | IMP, MER | ||||
| mexT | MexEF-OprN hyperproduction | FQ | Gain-of-function | G257S, G257A | Juarez et al., 2018 |
| OprD downregulation | IMP, MER | ||||
| cmrA | MexEF-OprN hyperproduction | MER, FQ | Gain-of-function | A68V, L89Q, H204L, N214K | Juarez et al., 2017 |
| mvaT | MexEF-OprN hyperproduction | FQ | Loss-of-function | ||
| PA3271 | MexEF-OprN hyperproduction | FQ | Loss-of-function | ||
| mexZ | MexXY-OprM hyperproduction | FQ, AMG, CEF | Loss-of-function | ||
| PA5471.1 | MexXY-OprM hyperproduction | FQ, AMG, CEF | Loss-of-function | ||
| amgS | MexXY-OprM hyperproduction | FQ, AMG, CEF | Gain-of-function | V121G, R182C | Lau et al., 2015 |
| oprD | OprD inactivation | IMP, MER | Loss-of-function | ||
| ampC | AmpC structural modification | CAZ/AVI, C/T | Gain-of-function | T96I, G183D, E247K | Cabot et al., 2014; Fraile-Ribot et al., 2017a |
| ampD | AmpC hyperproduction | CAZ, CEF, PPT | Loss-of-function | ||
| ampDh2 | AmpC hyperproduction | CAZ, CEF, PPT | Loss-of-function | ||
| ampDh3 | AmpC hyperproduction | CAZ, CEF, PPT | Loss-of-function | ||
| ampR | AmpC hyperproduction | CAZ, CEF, PPT | Gain-of-function | D135N, G154R | Bagge et al., 2002; Cabot et al., 2016b |
| dacB | AmpC hyperproduction | CAZ, CEF, PPT | Loss-of-function | ||
| ftsI | Penicillin-binding-protein 3 (PBP3) | CAZ, CEF, PPT, MER, CAZ/AVI, C/T | Gain-of-function | R504C, R504H, P527T, F533L | Diaz Caballero et al., 2015; Cabot et al., 2016a,b; Del Barrio-Tofiño et al., 2017; López-Causapé et al., 2017 |
| fusA1 | Elongation factor G | AMG | Gain-of-function | I61M, V93A, E100G, K504E, Y552C, P554L, A555E, N592I, P618L, T671A, T671I | Feng et al., 2016; Bolard et al., 2017; Del Barrio-Tofiño et al., 2017; López-Causapé et al., 2017, 2018 |
| glpT | Transporter protein GlpT | FOS | Loss-of-function | ||
| rpoB | RNA polymerase β-chain | RIF | Gain-of-function | S517F, Q518R, Q518L, D521G, H531Y, H531L, S536F, L538I, S579F, S579Y, N629S, D636Y | Jatsenko et al., 2010 |
aFQs, fluoroquinolones; COL, colistin; AMGs, aminoglycosides; CAZ, ceftazidime; CEF, cefepime; PPT, piperacillin-tazobactam; IMP, imipenem; MER, meropenem; CAZ/AVI, ceftazidime/avibactam; C/T, ceftolozane/tazobactam; FOS, fosfomycin; RIF, rifampicin.