Abstract
Vibrio cholerae must sense and respond appropriately to stresses encountered in the aquatic environment and the human host. One stress encountered in both environments is exposure to antimicrobial peptides (AMPs), produced as a part of the innate immune response by all multicellular organisms. Previous transcriptomic analysis demonstrated that expression of Stress-inducible protein A (SipA) (VCA0732), a hypothetical protein, was highly induced by AMP exposure and was dependent on a specific uncharacterized two-component system. In order to better understand role of this protein in stress relief, we examined whether it shared any of the phenotypes reported for its homologs. SipA is required for survival in the presence of two other stressors, cadmium chloride and hydrogen peroxide, and it localizes to the bacterial periplasm, similar to its homologs. We also found that SipA physically interacts with OmpA. Importantly, we found that SipA binds AMPs in the bacterial periplasm. This suggests a model where SipA may act as a molecular chaperone, binding AMPs that enter the periplasm and delivering them to OmpA for removal from the cell. While El Tor V. cholerae strains lacking SipA do not show a survival defect in the presence of AMPs, we found that Classical sipA mutants are less able to survive in the presence of AMPs. This phenotype is likely masked in the El Tor background due to a functional lipid A modification system that increases AMP resistance in these strains. In summary, we have identified a protein that contributes to a novel mechanism of stress relief in V. cholerae.