Lactonase Specificity Is Key to Quorum Quenching in Pseudomonas aeruginosa

Benjamin Remy (1, 2) , Laure Plener (1) , Philippe Decloquement (2, 3) , Nicholas Armstrong (2, 3) , Mikael Elias (4, 2, 3) , David Daudé (1) , Eric Chabriere (2, 3)

1 Gene&GreenTK
2 MEPHI - Microbes évolution phylogénie et infections
3 IHU Marseille - Institut Hospitalier Universitaire Méditerranée Infection
4 UMN - University of Minnesota [Twin Cities]

The human opportunistic pathogen Pseudomonas aeruginosa 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 N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C-12 HSL) and butyryl-homoserine lactone (C-4 HSL) albeit with different efficacies on C-4 HSL. Interestingly, both lactonases similarly decreased AHL concentrations and comparably impacted the expression of AHL-based QS genes. However, strong variations were observed in Pseudomonas Quinolone Signal (PQS) regulation depending on the lactonase used. Both lactonases were also found to decrease virulence factors production and biofilm formation in vitro, albeit with different efficiencies. Unexpectedly, only the lactonase with lower efficacy on C-4 HSL was able to inhibit P. aeruginosa pathogenicity in vivo 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 P. aeruginosa PA14.

Mots clés: quorum sensing; Pseudomonas aeruginosa; quorum quenching; acyl-homoserine lactones; lactonases; virulence; biofilm

Domaines: Sciences du Vivant [q-bio]

Benjamin Remy, Laure Plener, Philippe Decloquement, Nicholas Armstrong, Mikael Elias, et al.. Lactonase Specificity Is Key to Quorum Quenching in Pseudomonas aeruginosa. Frontiers in Microbiology, 2020, 11, ⟨10.3389/fmicb.2020.00762⟩. ⟨hal-03150170⟩