A multidrug resistant clinical P. aeruginosa isolate in the MLST550 clonal complex: uncoupled quorum sensing modulates the interplay of virulence and resistance

Abstract

Pseudomonas aeruginosa is a prevalent and pernicious pathogen equipped with both extraordinary capabilities to infect the host and to develop antimicrobials resistance (AMR). Monitoring the emergence of AMR high risk clones and understanding the interplay of their pathogenicity and antibiotic resistance is of paramount importance to avoid resistance dissemination and to control <P.aeruginosa infections. In this study, we report the identification of a multidrug resistant (MDR) P.aeruginosa strain PA154197 isolated from a blood stream infection in Hong Kong. PA154197 belongs to a distinctive MLST550 clonal complex shared by two international P.aeruginosa isolates VW0289 and AUS544. Comparative genome and transcriptome analysis with the reference strain PAO1 led to the identification of a variety of genetic variations in antibiotic resistance genes and the hyper-expression of three multidrug efflux pumps MexAB-OprM, MexEF-OprN, and MexGHI-OpmD in PA154197. Unlike many resistant isolates displaying an attenuated virulence, PA154197 produces a significantly high level of the P.aeruginosa major virulence factor pyocyanin (PYO) and displays an uncompromised virulence compared to PAO1. Further analysis revealed that the secondary quorum sensing system Pqs which primarily controls the PYO production is hyper-active in PA154197 independent of the master QS systems Las and Rhl. Together, these investigations disclose a unique, uncoupled QS mediated pathoadaptation mechanism inclinical P.aeruginosa which may account for the high pathogenic potentials and antibiotics resistance in the MDR isolate PA154197.