Effect of Quorum Quenching Lactonase in Clinical Isolates of Pseudomonas aeruginosa and Comparison with Quorum Sensing Inhibitors

• Published in: Frontiers in microbiology Vol. 8; p. 227
• Main Authors: Guendouze, Assia, Plener, Laure, Bzdrenga, Janek, Jacquet, Pauline, Rémy, Benjamin, Elias, Mikael, Lavigne, Jean-Philippe, Daudé, David, Chabrière, Eric
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media 14.02.2017; Frontiers Media S.A
• Subjects: Human health and pathology; Infectious diseases; Life Sciences; Microbiology; bacterial virulence; quorum sensing; anti-bacterial agents; lactonase; quorum quenching; biofilm; proteases; pyocyanin
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2017.00227

is a Gram negative pathogenic bacterium involved in many human infections including otitis, keratitis, pneumonia, and diabetic foot ulcers. uses a communication system, referred to as quorum sensing (QS), to adopt a group behavior by synchronizing the expression of certain genes. Among the regulated traits, secretion of proteases or siderophores, motility and biofilm formation are mainly involved in the pathogenicity. Many efforts have been dedicated to the development of quorum sensing inhibitors (QSI) and quorum quenching (QQ) agents to disrupt QS. QQ enzymes have been particularly considered as they may act in a catalytic way without entering the cell. Here we focus on the lactonase Pox which was previously investigated for its ability to degrade the signaling molecules, acyl-homoserine lactones, in particular on the engineered variant Pox-W263I. We highlight the potential of Pox-W263I to inhibit the virulence of 51 clinical isolates from diabetic foot ulcers by decreasing the secretion of two virulence factors, proteases and pyocyanin, as well as biofilm formation. We further compared the effect of Pox-W263I to the comprehensively described QSI, 5-fluorouracil and C-30. We found the lactonase Pox-W263I to be significantly more effective than the tested QSI at their respective concentration optimum and to retain its activity after immobilization steps, paving the way for future therapeutic applications.