Secretome analysis reveals a role of subinhibitory concentrations of polymyxin B in the survival of Vibrio cholerae mediated by the type VI secretion system

Abstract

Antimicrobials are commonly used in prevention of infections including in aquaculture, agriculture and medicine. Subinhibitory concentrations of antimicrobial peptides can modulate resistance, virulence and persistence effectors in Gram-negative pathogens. In this study, we investigated the effect of subinhibitory concentrations of polymyxin B (PmB) on the secretome of Vibrio cholerae, a natural inhabitant of aquatic environments and the pathogen responsible for the cholera disease. Our proteomic approach revealed that the abundance of many extracellular proteins is affected by PmB and some of them are detected only either in the presence or in the absence of PmB. The type VI secretion system (T6SS) secreted hemolysin-coregulated protein (Hcp) displayed an increased abundance in the presence of PmB. Hcp is also more abundant in the bacterial cells in the presence of PmB and hcp expression is upregulated upon PmB supplementation. No effect of the T6SS on antimicrobial resistance was observed. Conversely, PmB increases the T6SS-dependent cytotoxicity of V. cholerae towards the amoeba Dictyostelium discoideum and its ability to compete with Escherichia coli.