Aminoglycoside Resistance in<i>Pseudomonas aeruginosa</i>

Poole, Keith

doi:10.1128/aac.49.2.479-487.2005

Cited by 411 publications

(356 citation statements)

References 180 publications

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“…Aminoglycosides such as amikacin, gentamicin and tobramycin are a vital component of antipseudomonal chemotherapy for a variety of infections, particularly pulmonary infections in cystic fibrosis (CF) patients (Poole, 2005(Poole, , 2011. Aminoglycoside resistance in P. aeruginosa has often arisen via acquired aminoglycoside-modifying enzymes (AMEs) and 16S rRNA methylases (RMTs), typically involving the MexXY endogenous efflux system (Poole, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…Each AME has limited substrate specificity, but individual aminoglycoside-resistant P. aeruginosa isolates can carry multiple (2-5) AMEs and thus exhibit broad-spectrum aminoglycoside resistance (Poole, 2005). Among the AMEs, AAC(69)-II and ANT(299)-I are the most prevalent mechanisms for aminoglycoside resistance in P. aeruginosa (Armstrong & Miller, 2010;Poole, 2005). RMTs were recently discovered in P. aeruginosa (Yokoyama et al, 2003) and these promote high-level resistance to clinically used aminoglycosides, such as gentamicin, tobramycin and amikacin (Doi & Arakawa, 2007;Doi & Arakawa, 2007;Poole, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…MexXY-OprA of PA7 is a 'hybrid' system in that the PA7-specific oprA gene that is absent from the other known P. (Mugnier et al, 1998). This amino acid change has been associated with a shift from amikacin to gentamicin resistance in vitro after site-directed mutagenesis (Rather et al., 1992) and in various clinical isolates (Lambert et al, 1994;Mugnier et al, 1998;Casin et al, 2003;Poole, 2005). A recombinant Escherichia coli strain carrying AAC(69)-Ib 9 is strongly resistant to tobramycin and gentamicin and moderately (or slightly) resistant to amikacin (Rather et al, 1992;Casin et al, 2003).…”

mentioning

confidence: 99%

“…Henrichfreise Sekiguchi et al, 2007;Samuelsen et al, 2010;Poole, 2011). Each AME has limited substrate specificity, but individual aminoglycoside-resistant P. aeruginosa isolates can carry multiple (2-5) AMEs and thus exhibit broad-spectrum aminoglycoside resistance (Poole, 2005). Among the AMEs, AAC(69)-II and ANT(299)-I are the most prevalent mechanisms for aminoglycoside resistance in P. aeruginosa (Armstrong & Miller, 2010;Poole, 2005).…”

mentioning

confidence: 99%

“…The emergence and spread of multidrug-, extensive drug-and pan-drug-resistant P. aeruginosa infections are very serious and of great concern, as few agents are effective against these organisms. In addition, antibiotic-resistant Gram-negative bacteria, including P. aeruginosa, increase the hospital costs and length of stay associated with healthcare-associated infections (Mauldin et al, 2010).Aminoglycosides such as amikacin, gentamicin and tobramycin are a vital component of antipseudomonal chemotherapy for a variety of infections, particularly pulmonary infections in cystic fibrosis (CF) patients (Poole, 2005(Poole, , 2011. Aminoglycoside resistance in P. aeruginosa has often arisen via acquired aminoglycoside-modifying enzymes (AMEs) and 16S rRNA methylases (RMTs), typically involving the MexXY endogenous efflux system (Poole, 2011).…”

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confidence: 99%

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Primary mechanisms mediating aminoglycoside resistance in the multidrug-resistant Pseudomonas aeruginosa clinical isolate PA7

2012

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The multiresistant taxonomic outlier Pseudomonas aeruginosa PA7 possesses the conserved efflux genes, mexXY; however these are linked to a unique gene encoding an outer membrane channel, dubbed oprA, that is absent in most P. aeruginosa strains. Using genetic knockouts and single copy chromosomal complementation, we showed that aminoglycoside resistance in PA7 is mediated in part by the MexXY-OprA pump, and intriguingly that MexXY in this strain can utilize either the OprA or OprM outer membrane channel, linked to the mexAB efflux genes. We also identified a small portion of the oprA gene immediately downstream of the mexY gene in PAO1, suggesting that non-PA7 P. aeruginosa strains might have possessed, but lost, the intact mexXYoprA efflux pump locus. Consistent with this, most of a panel of serotype strains possessed the truncated oprA but the serotype O12 isolate had an intact mexXY-oprA locus, similar to PA7 and the related strain DSM 1128. We also showed that the mexZ repressor gene upstream of mexXYoprA in PA7 is mutated, leading to overexpression of mexXY-oprA, using sequencing, homologous replacement and real-time quantitative reverse transcriptase PCR. Finally we assessed the contribution of MexXY and aminoglycoside modifying enzymes AAC together to resistance in PA7 and the AAC(69)-Iae-mediated amikacin-resistant clinical isolate IMCJ2.S1, concluding that the effect of the modifying enzymes is enhanced by functional efflux, especially in the presence of divalent cations, to develop high-level aminoglycoside resistance in P. aeruginosa. INTRODUCTIONPseudomonas aeruginosa is a common nosocomial pathogen that causes a broad range of infections with a high mortality rate (Mahar et al., 2010; Iida et al., 2010;Lambert et al., 2011). A major factor in its prominence as a pathogen is, in part, its intrinsic resistance to a number of antibacterial agents (Poole et al., 1993;Hancock, 1998;Poole, 2002) and, particularly, the development of increased multidrug resistance in healthcare settings (Giamarellos-Bourboulis et al., 2006;Kirikae et al., 2008;Kallen et al., 2010;Keen et al., 2010). This organism readily acquires resistance via chromosomal mutations (e.g. overexpression of the efflux pump) and lateral gene transfer (e.g. acquisition of metallob-lactamase) (Lister et al., 2009;Poole, 2011). The emergence and spread of multidrug-, extensive drug-and pan-drug-resistant P. aeruginosa infections are very serious and of great concern, as few agents are effective against these organisms. In addition, antibiotic-resistant Gram-negative bacteria, including P. aeruginosa, increase the hospital costs and length of stay associated with healthcare-associated infections (Mauldin et al., 2010).Aminoglycosides such as amikacin, gentamicin and tobramycin are a vital component of antipseudomonal chemotherapy for a variety of infections, particularly pulmonary infections in cystic fibrosis (CF) patients (Poole, 2005(Poole, , 2011. Aminoglycoside resistance in P. aeruginosa has often arisen via acquired aminoglycoside-modifyi...

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Section: Introductionmentioning

confidence: 99%