A novel role of VisP and the Wzz system during O-antigen assembly inSalmonellaTyphimurium pathogenesis

Abstract

AbstractSalmonella entericaserovars are associated with diarrhea and gastroenteritis and are a helpful model for understanding host-pathogen mechanisms.SalmonellaTyphimurium 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 ofSalmonella-containing vacuoles (SCVs). The virulence and stress-related periplasmic protein (VisP) participates in OAg synthesis, as ΔvisPpresents a semirough OAg phenotype. The ΔvisPmutant has greatly decreased motility and J774 macrophage survival in a colitis model of infection. Interestingly, the phenotype is restored after mutation of thewzzSTorwzzfepEgene in a ΔvisPbackground. Loss of both thevisPandwzzSTgenes 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 duringS.Typhimurium pathogenesis and show the periplasmic protein VisP as a novel protein in the OAg biosynthesis pathway.Author summarySalmonellamodifies 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, improvingSalmonellapathogenesis. 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.