Abstract
TIR domain-containing proteins are essential for bacterial pathogens to subvert host defenses. This study describes a fish pathogen, Yersinia ruckeri SC09 strain, with a novel TIR domain-containing protein (STIR-2) that affects Toll-like receptor (TLR) function. STIR-2 was identified in Y. ruckeri by bioinformatics analysis. The toxic effects of this gene on fish were determined by in vivo challenge experiments in knockout mutants and complement mutants of the stir-2 gene. In vitro, STIR-2 downregulated the expression and secretion of IL-6, IL-1β, and TNF-α. Furthermore, the results of NF-κB-dependent luciferase reporter system, co-immunoprecipitation, GST pull-down assays, and yeast two-hybrid assay indicated that STIR-2 inhibited the TLR signaling pathway by interacting with myeloid differentiation factor 88 (MyD88). In addition, STIR-2 promoted the intracellular survival of pathogenic Yersinia ruckeri SC09 strain by binding to the TIR adaptor protein MyD88 and inhibiting the pre-inflammatory signal of immune cells. These results showed that STIR-2 increased virulence in Y. ruckeri and suppressed the innate immune response by inhibiting TLR and MyD88-mediated signaling, serving as a novel strategy for innate immune evasion.
Highlights
Virulence factors are extracellular proteins produced by pathogens to establish and maintain disease
A bacterial protein homologous to the Toll/IL-1 receptor (TIR) domain encoded by SC09-integrative and conjugative elements (ICEs)(r2), which acts as an accessory gene, has been identified
Gene clusters associated with pathogenicity and bacterial survival may be distributed over longer loci, such as genes encoding capsular polysaccharides [39] or lipopolysaccharides [40], or larger polyprotein devices such as the type 3 secretion system (T3SS) [41]
Summary
Virulence factors are extracellular proteins produced by pathogens to establish and maintain disease. Most virulence factors are enzymes that promote the growth and development of pathogens. Streptococcus [1], Staphylococcus [2], and Clostridium [3] produce hyaluronidase, which promotes microbial growth in tissues by hydrolyzing hyaluronic acid. Streptococcus and Staphylococcus produce large amounts of proteolytic enzymes [4], nucleases [5], and lipases [6] that depolymerize host proteins, nucleic acids, and fats, respectively. The host interacts with extracellular proteins to reduce their likelihood of causing disease [7,8]. In addition to virulence factors, genes involved in bacterial viability are a cause for concern because they help bacteria adapt to several living environments (including survival in the host and other cells). The contribution of force may be more stable and lasting
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