Role of Yersinia pestis toxin complex family proteins in resistance to phagocytosis by polymorphonuclear leukocytes.

Yersinia pestis carries homologues of the toxin complex (Tc) family proteins, which were first identified in other Gram-negative bacteria as having potent insecticidal activity. The Y. pestis Tc proteins are neither toxic to fleas nor essential for survival of the bacterium in the flea, even though tc gene expression is highly upregulated and much more of the Tc proteins YitA and YipA are produced in the flea than when Y. pestis is grown in vitro. We show that Tc(+) and Tc(-) Y. pestis strains are transmitted equivalently from coinfected fleas, further demonstrating that the Tc proteins have no discernible role, either positive or negative, in transmission by the flea vector. Tc proteins did, however, confer Y. pestis with increased resistance to killing by polymorphonuclear leukocytes (PMNs). Resistance to killing was not the result of decreased PMN viability or increased intracellular survival but instead correlated with a Tc protein-dependent resistance to phagocytosis that was independent of the type III secretion system (T3SS). Correspondingly, we did not detect T3SS-dependent secretion of the native Tc proteins YitA and YipA or the translocation of YitA- or YipA-β-lactamase fusion proteins into CHO-K1 (CHO) cells or human PMNs. Thus, although highly produced by Y. pestis within the flea and related to insecticidal toxins, the Tc proteins do not affect interaction with the flea or transmission. Rather, the Y. pestis Tc proteins inhibit phagocytosis by mouse PMNs, independent of the T3SS, and may be important for subverting the mammalian innate immune response immediately following transmission from the flea.