AUTHOR=Rémy Benjamin , Plener Laure , Decloquement Philippe , Armstrong Nicholas , Elias Mikael , Daudé David , Chabrière Éric 

TITLE=Lactonase Specificity Is Key to Quorum Quenching in Pseudomonas aeruginosa

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.00762

DOI=10.3389/fmicb.2020.00762

ISSN=1664-302X

ABSTRACT=<p>The human opportunistic pathogen <italic>Pseudomonas aeruginosa</italic> orchestrates the expression of many genes in a cell density-dependent manner by using quorum sensing (QS). Two acyl-homoserine lactones (AHLs) are involved in QS circuits and contribute to the regulation of virulence factors production, biofilm formation, and antimicrobial sensitivity. Disrupting QS, a strategy referred to as quorum quenching (QQ) can be achieved using exogenous AHL-degrading lactonases. However, the importance of enzyme specificity on quenching efficacy has been poorly investigated. Here, we used two lactonases both targeting the signal molecules <italic>N</italic>-(3-oxododecanoyl)-<sc>L</sc>-homoserine lactone (3-oxo-C<sub>12</sub> HSL) and butyryl-homoserine lactone (C<sub>4</sub> HSL) albeit with different efficacies on C<sub>4</sub> HSL. Interestingly, both lactonases similarly decreased AHL concentrations and comparably impacted the expression of AHL-based QS genes. However, strong variations were observed in <italic>Pseudomonas</italic> Quinolone Signal (PQS) regulation depending on the lactonase used. Both lactonases were also found to decrease virulence factors production and biofilm formation <italic>in vitro</italic>, albeit with different efficiencies. Unexpectedly, only the lactonase with lower efficacy on C<sub>4</sub> HSL was able to inhibit <italic>P. aeruginosa</italic> pathogenicity <italic>in vivo</italic> in an amoeba infection model. Similarly, proteomic analysis revealed large variations in protein levels involved in antibiotic resistance, biofilm formation, virulence and diverse cellular mechanisms depending on the chosen lactonase. This global analysis provides evidences that QQ enzyme specificity has a significant impact on the modulation of QS-associated behavior in <italic>P. aeruginosa</italic> PA14.</p>