The Yersinia pestis type III secretion system (T3SS) functions to inject anti-host proteins, termed Yops, directly into the cytoplasm of targeted eukaryotic cells. The injection process can be divided into three distinct steps: (i) attachment of the bacteria to a eukaryotic cell;(ii) secretion of Yops across the bacterial inner and outer membranes;and (iii) translocation of Yops across a eukaryotic membrane. Work in our laboratory supported by this Grant has focused on the regulation of the T3S process. Yop secretion is triggered by contact with a eukaryotic cell in vivo or by growth in the absence of extracellular calcium in vitro. A cytosolic YopN/SycN/YscB/TyeA complex is required to block Yop secretion in the presence of calcium and prior to contact with a eukaryotic cell. The mechanism by which the bacterium senses these extracellular signals and transmits this information to the cytosolic compartment is not known. We have recently demonstrated that the surface-localized YscF needle is required to regulate Yop secretion. We hypothesize that the YscF needle and needle-associated proteins (the LcrV needle tip complex and Yscl rod structure) function, in part, to sense extracellular signals, transmit this information to the cytosolic compartment and regulate the activity of a molecular plug (the YopN/SycN/YscB/TyeA complex). The proposed research is aimed at gaining a better understanding of the regulatory events that control Yop secretion. Specifically, we will (i) elucidate the molecular mechanism by which the YopN/SycN/YscB/TyeA complex blocks secretion and (ii) investigate the role of the Yscl rod, the YscF needle and the LcrV tip complex in the regulation of Yop secretion. These studies will advance our understanding of the molecular events that regulate T3S in Y. pestis and in other important pathogens.
|Chen, Yi-Shan; Bastidas, Robert J; Saka, Hector A et al. (2014) The Chlamydia trachomatis type III secretion chaperone Slc1 engages multiple early effectors, including TepP, a tyrosine-phosphorylated protein required for the recruitment of CrkI-II to nascent inclusions and innate immune signaling. PLoS Pathog 10:e1003954|
|Minato, Yusuke; Ghosh, Amit; Faulkner, Wyatt J et al. (2013) Na+/H+ antiport is essential for Yersinia pestis virulence. Infect Immun 81:3163-72|
|Chaudhury, Sukanya; Battaile, Kevin P; Lovell, Scott et al. (2013) Structure of the Yersinia pestis tip protein LcrV refined to 1.65?Å resolution. Acta Crystallogr Sect F Struct Biol Cryst Commun 69:477-81|
|Joseph, Sabrina S; Plano, Gregory V (2013) The SycN/YscB chaperone-binding domain of YopN is required for the calcium-dependent regulation of Yop secretion by Yersinia pestis. Front Cell Infect Microbiol 3:1|
|Bartra, Sara Schesser; Gong, Xin; Lorica, Cherish D et al. (2012) The outer membrane protein A (OmpA) of Yersinia pestis promotes intracellular survival and virulence in mice. Microb Pathog 52:41-6|
|Bartra, Sara Schesser; Styer, Katie L; O'Bryant, Deanna M et al. (2008) Resistance of Yersinia pestis to complement-dependent killing is mediated by the Ail outer membrane protein. Infect Immun 76:612-22|
|Styer, Katie L; Hopkins, Gregory W; Bartra, Sara Schesser et al. (2005) Yersinia pestis kills Caenorhabditis elegans by a biofilm-independent process that involves novel virulence factors. EMBO Rep 6:992-7|