Role of efflux pumps: MexAB-OprM and MexXY(-OprA), AmpC cephalosporinase and OprD porin in non-metallo-β-lactamase producing Pseudomonas aeruginosa isolated from cystic fibrosis and burn patients.

PURPOSE OF THE RESEARCH: In order to gain a better understanding of the role of several mechanisms in antibiotic resistance in Pseudomonas aeruginosa clinical isolates obtained from CF and burn patients, we evaluated gene expression of efflux pumps MexAB-OprM and MexXY(-OprA), the natural β-lactamase AmpC and outer membrane porin protein OprD. Also, the presence of genes encoding Ambler classes A, B β-lactamases and aminoglycoside modifying enzymes (AMEs) was examined.

PRINCIPAL RESULTS: Piperacillin-tazobactam and amikacin retained the highest in vitro activities among 21 CF and 27 burn P. aeruginosa isolates. Based on Enterobacterial Repetitive Intergenic Consensus (ERIC) PCR, 15 distinct patterns were detected. There were 5 CF and 6 burn isolates harbored PER-1 and VEB-1, respectively. Among AMEs, involved in resistance of anti-Pseudomonas aminoglycosides, aac(6')-Ib was the most prevalent gene. Among CF isolates, mexA overexpression was the most prevalent mechanism (47.6%) followed by mexX (42.8%), ampC (9.5%) and oprD downregulation (4.7%). Among burn isolates, the prevalence of mexX, mexA, and ampC overexpression was 62.9%, 74%, and 11.1%, respectively. Downregulation of oprD was observed in 14.8% of burn isolates.

MAJOR CONCLUSIONS: Among CF isolates, mexX and mexA overexpression were the major contributing factors to aminoglycoside (gentamicin) and carbapenem (meropenem) resistance, respectively while among burn isolates, AMEs in conjunction with mexX hyperexpression were identified to be responsible for aminoglycoside resistance. Also mexA overexpression was partially associated with carbapenem resistance. Moreover, cephalosporin resistance was linked to overexpression of mexA and/or mexX. The impact of interplay between different resistance mechanisms on resistant phenotypes was more complicated among burn than CF isolates.