Mammalian-Specificity in TC Toxins Found in Yersinia pestis and Yersinia pseudotuberculosis

Abstract

Toxin complex family proteins (TC toxins) are a family of large, tripartite, high molecular weight, traditionally insecticidal toxins operating through a syringe-like mechanism; comprised of a bell-shaped subunit A and a chamber formed from subunit B and C situated above a translocation channel within subunit A. First identified in Photorhabdus luminescens, homologs of TC toxins can be found within several insect pathogen bacteria, all sharing similar structure and mechanism. In recent years, evidence of an insecticidal-like form of TC toxin with mammalian-specific toxicity has emerged in Yersinia pseudotuberculosis and Yersinia pestis. These insecticidal-like deviations of TC toxins exhibit reduction in insect toxicity and display toxicity towards mammalian cells. Within Y. pestis, TC toxin has gained further distinct qualities such as preferential gene upregulation in flea vectors, null toxicity towards flea vectors, lack of contribution to transmission quality, and inhibition of phagocytosis immediately following transmission. If Y. pestis TC toxin T3SS (type III secretion system) independence can be conclusively determined, the current data suggests Y. pestis TC toxin may serve as an interval bridge providing phagocytosis resistance prior to the T3SS temperature-shift process.