Surface of Yersinia pestis: LCRV, F1 Production, Invasion and Oxygen: A Dissertation

Abstract

Of the eleven species of bacteria that comprise the genus Yersinia of the family Enterobacteriaceae three speCIes are pathogenic for humans. Yersinia pseudotuberculosis and Yersinia enterocolitica usually cause a mild, self-limiting mesenteric lymphadenitis or ileitis. Yersinia pestis causes a highly invasive often fatal disease known as plague. All three elaborate a type three secretion system that is essential for virulence and encoded on closely related plasmids. In Y pestis all the effectors, structural components and chaperones are encoded on the 70kb plasmid, pCD I. Of these , LcrV from enterocolitica has been implicated in playing an immunosuppressive role through its interaction with host Toll-like receptor 2 (TLR2) and induction of ILIO. Through expression and purification of recombinant LcrV from Escherichia coli we show that only high molecular weight species of rLcrV are able to stimulate TLR2. In a highly sensitive subcutaneous mouse infection model we demonstrate no difference in the time to death between TLR2-sufficient or deficient mice. Analysis of cytokine levels between these two genotypes also shows no significant difference between splenic ILIO and IL-6 or levels of bacteria. We conclusively show that this interaction, if it does occur, plays no significant role in vivo. In a separate set of experiments , we also determined that the expression of , a peptide shown to be responsible for 37 dependent inhibition of invasion by pestis in vitro was significantly decreased under high oxygen conditions. This led us to re-examine the invasion phenotype both in vitro and in vivo. These results give new insights into virulence gene expression in Y pestis by environmental cues other than