Abstract
Pseudomonas aeruginosa is a Gram negative pathogenic bacterium involved in many human infections including otitis, keratitis, pneumonia, and diabetic foot ulcers. P. aeruginosa 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 SsoPox which was previously investigated for its ability to degrade the signaling molecules, acyl-homoserine lactones, in particular on the engineered variant SsoPox-W263I. We highlight the potential of SsoPox-W263I to inhibit the virulence of 51 clinical P. aeruginosa 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 SsoPox-W263I to the comprehensively described QSI, 5-fluorouracil and C-30. We found the lactonase SsoPox-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.
Highlights
Pseudomonas aeruginosa is a human opportunistic pathogen involved in many infection types and which causes serious health complications (Stover et al, 2000; Driscoll et al, 2012)
We investigated the effectiveness of the quorum quenching (QQ) enzyme SsoPox-W263I, a variant of SsoPox with increased catalytic effectiveness against 3-oxo-C12 acyl-homoserine lactone (AHL) (Hiblot et al, 2013; Rémy et al, 2016b), previously reported as being efficient to drastically reduce the mortality in a rat pneumonia model (Hraiech et al, 2014), to modulate virulence factors in 51 clinical P. aeruginosa isolates collected from diabetic foot ulcers
Pseudomonas aeruginosa model strains PAO1 and PA14 were used to determine the optimal concentrations of the QQ enzyme SsoPox and the quorum sensing inhibitors (QSI) 5-FU and C-30 to decrease virulence factor production
Summary
Pseudomonas aeruginosa is a human opportunistic pathogen involved in many infection types and which causes serious health complications (Stover et al, 2000; Driscoll et al, 2012). Regarding the importance of bacterial communication in the development of virulence, strategies for QS disruption, known as quorum quenching (QQ), have emerged to maintain bacteria in a commensal lifestyle To this end, quorum sensing inhibitors (QSI) and QQ enzymes have been considered (Dong et al, 2007; Kalia, 2013; Tang and Zhang, 2014; Brackman and Coenye, 2015; Fetzner, 2015). We compared its QQ potential to the most common QSI, the brominated furanone C-30 and the pyrimidine analog 5-fluorouracil (5-FU), by quantifying three virulence factors: pyocyanin production, protease secretion and biofilm formation (Ren et al, 2001; Ueda et al, 2009).
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