1887

Abstract

The multiresistant taxonomic outlier PA7 possesses the conserved efflux genes, ; however these are linked to a unique gene encoding an outer membrane channel, dubbed , that is absent in most 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 efflux genes. We also identified a small portion of the gene immediately downstream of the gene in PAO1, suggesting that non-PA7 strains might have possessed, but lost, the intact efflux pump locus. Consistent with this, most of a panel of serotype strains possessed the truncated but the serotype O12 isolate had an intact locus, similar to PA7 and the related strain DSM 1128. We also showed that the repressor gene upstream of in PA7 is mutated, leading to overexpression of , 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(6′)-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 .

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2012-04-01
2019-12-10
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