Comprehension of Antimicrobial Peptides Modulation of the Type VI Secretion System in Vibrio cholerae

The Type VI secretion System (T6SS) is a versatile weapon used by bacteria for virulence, resistance to grazing and competition with other bacteria. We previously demonstrated that the role of the T6SS in interbacterial competition and in resistance to grazing is enhanced in Vibrio cholerae in the presence of subinhibitory concentrations of polymyxin B (PmB). In this study, we performed a global quantitative proteomic analysis by liquid chromatography coupled to mass spectrometry and a transcriptomic analysis by quantitative PCR of the T6SS known regulators in V. cholerae grown with and without PmB. The proteome of V. cholerae is greatly modified in the presence of PmB at subinhibitory concentrations with more than 39 % of the identified cellular proteins displaying a difference in their abundance, including T6SS-related proteins (Hcp, VasC, TsaB and ClpV). We identified a regulator whose abundance and expression are increased in the presence of PmB, vxrB, the response regulator of the two-component system VxrAB. In a vxrAB deficient mutant, the expression of hcp measured by quantitative PCR, although globally reduced, was not modified in the presence of PmB, confirming its role in hcp upregulation with PmB. The upregulation of the T6SS in the presence of PmB appears to be, at least in part, due to the two-component system VxrAB. ImportanceThe type VI secretion system is important for bacterial competition, virulence and resistance to grazing by predators. In this study, we investigated the regulation leading to the type VI secretion system activation in the presence of polymyxin B (PmB), an antimicrobial used in veterinary and human health to treat infection caused by multi-resistant Gram-negative bacteria, in V. cholerae. In addition to making an overall portrait of the modifications to the proteome, we identified the VxrAB two-component system as the main regulator responsible for this activation. Our results provide evidence that subinhibitory concentrations of antimicrobials are responsible for important modifications of the proteome of pathogenic bacteria, inducing the production of proteins involved in virulence, host colonisation, resistance and environmental survival.