A novel role of VisP and Wzz system during O-antigen assembly in Salmonella Typhimurium pathogenesis

Abstract

Salmonella enterica serovars are associated with diarrhea and gastroenteritis and are a helpful model for understanding host-pathogen mechanisms. Salmonella Typhimurium regulates the distribution of O-antigen (OAg) and presents a trimodal distribution based on Wzy polymerase, WzzST (long chain length OAg, L-OAg) and WzzfepE (very long chain length OAg, VL-OAg) co-polymerases; however, several mechanisms regulating this process remain unclear. Here, we report that LPS modifications modulate the infectious process and that OAg chain length determination plays an essential role during infection. An increase in VL-OAg is dependent on Wzy polymerase, which is promoted by a growth condition resembling the environment of Salmonella-containing vacuoles (SCVs). The virulence and stress-related periplasmic protein (VisP) participates in OAg synthesis, as {Delta}visP presents a semirough OAg phenotype. The {Delta}visP mutant has greatly decreased motility and J774 macrophage survival in a colitis model of infection. Interestingly, the phenotype is restored after mutation of the wzzST or wzzfepE gene in a {Delta}visP background. Loss of both the visP and wzzST genes promotes an imbalance in flagellin secretion. L-OAg may function as a shield against host immune systems in the beginning of an infectious process, and VL-OAg protects bacteria during SCV maturation and facilitates intramacrophage replication. Taken together, these data highlight the roles of OAg length in generating phenotypes during S. Typhimurium pathogenesis and show the periplasmic protein VisP as a novel protein in the OAg biosynthesis pathway.\n\nAuthor summarySalmonella modifies its LPS, specifically the O-antigen length, to adapt itself to distinct intestinal environments. These LPS modifications may provide a way for this bacterium to avoid complement activation in the intestinal lumen, improving Salmonella pathogenesis. This process is essential for a successful infection, and our investigation into these specific details regarding LPS in this foodborne pathogen will elucidate different aspects of the host-pathogen association.