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Antimicrob Agents Chemother,
2019]
<i>Pseudomonas aeruginosa</i> is a prevalent and pernicious pathogen equipped with extraordinary capabilities both to infect the host and to develop antimicrobial 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 <i>P. aeruginosa</i> infections. In this study, we report the identification of a multidrug-resistant (MDR) <i>P. aeruginosa</i> strain PA154197 isolated from a blood stream infection in Hong Kong. PA154197 belongs to a distinctive MLST550 clonal complex shared by two other international <i>P. aeruginosa</i> isolates VW0289 and AUS544. Comparative genome and transcriptome analysis of PA154197 with the reference strain PAO1 led to the identification of a variety of genetic variations in antibiotic resistance genes and the hyperexpression of three multidrug efflux pumps MexAB-OprM, MexEF-OprN, and MexGHI-OpmD in PA154197. Unexpectedly, the strain does not display a metabolic cost and a compromised virulence compared to PAO1. Characterizing its various physiological and virulence traits demonstrated that PA154197 produces a substantially higher level of the <i>P. aeruginosa</i> major virulence factor pyocyanin (PYO) than PAO1, but it produces a decreased level of pyoverdine and displays decreased biofilm formation compared with PAO1. Further analysis revealed that the secondary quorum-sensing (QS) system Pqs that primarily controls the PYO production is hyperactive in PA154197 independent of the master QS systems Las and Rhl. Together, these investigations disclose a unique, uncoupled QS mediated pathoadaptation mechanism in clinical <i>P. aeruginosa</i> which may account for the high pathogenic potentials and antibiotic resistance in the MDR isolate PA154197.