Contribution of the MexXY multidrug efflux pump and other chromosomal mechanisms on aminoglycoside resistance in Pseudomonas aeruginosa isolates from canine and feline infections.
As study of multidrug efflux pumps is a crucial step for development of efflux pump inhibitors for treatment of Pseudomonas aeruginosa infection, the objective of this study was to examine the contribution of the MexXY multidrug efflux systems and other chromosomal mechanisms in aminoglycoside (AMG) resistance in P. aeruginosa isolated from dogs and cats. Thirteen Pseudomonas aeruginosa isolates from canine and feline infections were examined for contribution of the MexXY multidrug efflux pump and four other chromosomally-encoded genes including PA5471, galU, nuoG and rplY to AMG resistance. All the isolates were resistant to multiple AMGs and expressed mexXY. Deletion of mexXY caused 2- to 16-fold reduction in AMG MICs. Overproduction of MexXY did not fully account for the observed AMG resistance. No good correlations were detected between MexXY transcription level and AMG MICs. While no mutations were found in mexZ, PA5471 expression varied and its impact on MexXY expression and AMG resistance is diverse. No mutations were found in galU. Only two isolates carried a single base change G-367-T in rplY. Complete transcription of nuoG was detected in all the isolates. In conclusion, the MexXY multidrug efflux pump plays a role in AMG resistance in the dog and cat P. aeruginosa isolates, while disruption of nuoG, rplY and galU did not have a significant impact. These results indicate the existence of uncharacterized AMG-resistance mechanisms.
Department of Veterinary Public Health, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.
Kanchana
K
Poonsuk
Rungtip
R
Chuanchuen
D000617:Aminoglycosides / Q000494:pharmacology*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002371:Cat Diseases / Q000188:drug therapy / Q000382:microbiology*; D002415:Cats; D017931:DNA Primers / Q000235:genetics; D004283:Dog Diseases / Q000188:drug therapy / Q000382:microbiology*; D004285:Dogs; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000662:veterinary*; D011550:Pseudomonas aeruginosa; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary
D000617:Aminoglycosides; D001426:Bacterial Proteins; D017931:DNA Primers; C402791:MexXY protein, Pseudomonas aeruginosa