title: Effect of Quorum Quenching Lactonase in Clinical Isolates ofPseudomonas aeruginosaand Comparison with Quorum Sensing Inhibitors.
abstract: Pseudomonas aeruginosais a Gram negative pathogenic bacterium involved in many human infections including otitis, keratitis, pneumonia, and diabetic foot ulcers.P. aeruginosauses 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 lactonaseSsoPox which was previously investigated for its ability to degrade the signaling molecules, acyl-homoserine lactones, in particular on the engineered variantSsoPox-W263I. We highlight the potential ofSsoPox-W263I to inhibit the virulence of 51 clinicalP. aeruginosaisolates 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 ofSsoPox-W263I to the comprehensively described QSI, 5-fluorouracil and C-30. We found the lactonaseSsoPox-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.
authors.affiliation: URMITE, Aix-Marseille Université UM63, CNRS 7278, IRD 198, INSERM 1095 IHU - Méditerranée InfectionMarseille, France; Laboratoire de Biologie Moléculaire et Cellulaire, Université des frères Mentouri ConstantineConstantine, Algérie.
authors.forename: Assia
authors.initials: A
authors.lastname: Guendouze
authors.affiliation: Gene&GreenTK Marseille, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Plener
authors.affiliation: URMITE, Aix-Marseille Université UM63, CNRS 7278, IRD 198, INSERM 1095 IHU - Méditerranée Infection Marseille, France.
authors.forename: Janek
authors.initials: J
authors.lastname: Bzdrenga
authors.affiliation: URMITE, Aix-Marseille Université UM63, CNRS 7278, IRD 198, INSERM 1095 IHU - Méditerranée Infection Marseille, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Jacquet
authors.affiliation: URMITE, Aix-Marseille Université UM63, CNRS 7278, IRD 198, INSERM 1095 IHU - Méditerranée InfectionMarseille, France; Gene&GreenTKMarseille, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rémy
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics and Biotechnology Institute, University of Minnesota, St. Paul MN, USA.
authors.forename: Mikael
authors.initials: M
authors.lastname: Elias
authors.affiliation: INSERM, U1047, University of Montpellier 1Montpellier, France; Department of Microbiology, Caremeau University HospitalNîmes, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Lavigne
authors.affiliation: Gene&GreenTK Marseille, France.
authors.forename: David
authors.initials: D
authors.lastname: Daudé
authors.affiliation: URMITE, Aix-Marseille Université UM63, CNRS 7278, IRD 198, INSERM 1095 IHU - Méditerranée Infection Marseille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Chabrière
keywords: anti-bacterial agents; bacterial virulence; biofilm; lactonase; proteases; pyocyanin; quorum quenching; quorum sensing