Toll/IL-1 receptor-containing proteins STIR-1, STIR-2 and STIR-3 synergistically assist Yersinia ruckeri SC09 immune escape.

Immune escape is a common feature of bacteria, viruses, parasites and even cancer cells. Our earlier work on an integrative and conjugative element (ICEr2) of Yersinia ruckeri SC09 demonstrated contributory roles of stir-1, stir-2 and stir-3 in bacterial toxicity and ability to code for immune evasion. Here, we further examined the ability of stir-4 in ICE (r2) and its encoded STIR-4 protein to mediate immune evasion using comparative genomic analysis. Additionally, the mechanisms underlying the synergistic activities of STIR-1, STIR-2, STIR-3 and STIR-4 in immune evasion were examined. Our results showed that STIR-4 did not contribute to bacterial toxicity, either in vivo nor in vitro, or show the ability to assist in bacterial immune escape. STIR-1, STIR-2, and STIR-3 formed heterotrimers in bacteria while facilitating immune evasion, which we speculate may be essential to maintain their stability. This discovery also partially explains the previous finding that a single gene can mediate immune evasion. Our data provide further knowledge on the distribution of ICE (r2)-like elements in bacteria, validating the prevalence of large-scale gene transfer in pathogens and its potential for enhancing virulence levels. Further studies are necessary to establish the biological significance of the ICE (r2) component.