Lactonase-mediated inhibition of quorum sensing largely alters phenotypes, proteome, and antimicrobial activities in Burkholderia thailandensis E264

Abstract

IntroductionBurkholderia thailandensis is a study model for Burkholderia pseudomallei, a highly virulent pathogen, known to be the causative agent of melioidosis and a potential bioterrorism agent. These two bacteria use an (acyl-homoserine lactone) AHL-mediated quorum sensing (QS) system to regulate different behaviors including biofilm formation, secondary metabolite productions, and motility.MethodsUsing an enzyme-based quorum quenching (QQ) strategy, with the lactonase SsoPox having the best activity on B. thailandensis AHLs, we evaluated the importance of QS in B. thailandensis by combining proteomic and phenotypic analyses.ResultsWe demonstrated that QS disruption largely affects overall bacterial behavior including motility, proteolytic activity, and antimicrobial molecule production. We further showed that QQ treatment drastically decreases B. thailandensis bactericidal activity against two bacteria (Chromobacterium violaceum and Staphylococcus aureus), while a spectacular increase in antifungal activity was observed against fungi and yeast (Aspergillus niger, Fusarium graminearum and Saccharomyces cerevisiae).DiscussionThis study provides evidence that QS is of prime interest when it comes to understanding the virulence of Burkholderia species and developing alternative treatments.

AHL-Based Quorum Sensing Regulates the Biosynthesis of a Variety of Bioactive Molecules in Bacteria

“…Transcriptomic and proteomic studies showed that around 6% and 3% in P. aeruginosa and 9% and 18% in B. thailandensis, respectively, are impacted. Similarly, the expression of 12% of the V. campbellii transcriptome is modified upon QS, affecting many cellular functions (e.g., primary metabolism, motility, secretion systems). ,,− Among these important changes, modulations in the synthesis of secondary metabolites have been identified. Bacteria live in communities in conditions where nutrients can be scarce.…”

“… Bactobolin was identified because of its antimicrobial activity against a broad range of bacteria including Bacillus subtilis , , Bacillus cereus , Chromobacterium violaceum , Staphylococcus aureus , and Escherichia coli and antifungal activity against Candida krusei. Bactobolin inhibits protein synthesis by binding to the 50S ribosomal subunit in proximity to the L2 protein. ,− Besides its antimicrobial effects, 1 was reported to have antitumor activity in vitro on different cell types , and in vivo in murine models. , A recent study demonstrated that the disruption of QS considerably altered the proteome of B. thailandensis E264, including the biosynthesis of bactobolin molecules, as well as various secondary metabolites such as 4-hydroxy-3-methyl-2-alkenylquinoline (HMAQ; 2 ) and its derivatives, whose production was considerably impacted …”