The ability to enter, survive, and multiply within animal cells is a property common to many pathogens. To date each system that has been investigated has exhibited unique features. The simplest system is that of Yersinia pseudotuberculosis (Yp) and Y. enterocolitica (Ye), where individual invasion factors (either invasin, Ail, or YadA) are sufficient to confer the invasive phenotype to Escherichia coli. The long-term goals of this work are to understand the bacteria-host interaction at the molecular level, and to determine how the invasion process is coordinated with other aspects of Yersinia pathogenesis. Ye is an excellent model system for studying these questions because (a) it can be readily grown and manipulated genetically in the laboratory, (b) it has strong, well defined phenotypes in the in vitro assays, and (c) an excellent murine model of infection exists.
The SPECIFIC AIMS of this proposal are an extension of work already underway in the PI's lab.
AIM 1. How are Ail and the ail locus involved in interactions with the host and host cell? Experiments proposed in this section are aimed at further elucidating the functional domains of Ail and at identifying the host cell receptor for Ail. The PI plans to extend studies investigating the role of Ail during an infection, by using a rabbit model. In addition, in vivo studies of an ail yadA double mutant suggested that a locus near ail affects bacterial survival and this will be investigated further.
AIM 2. What is the basis for the difference in virulence of Ye and Yp yadA mutants? The Ye yadA mutant is avirulent while the Yp yadA mutant is almost fully virulent, suggesting Yp has a factor that compensates for the loss of YadA. Here the PI proposes to identify and characterize this factor(s).
AIM 3. How is inv regulated? The PI has identified a mutation that affects the temperature regulation of inv expression. She proposes to identify and characterize this regulator and how it affects inv expression. If time permits, she also hopes to do preliminary studies to investigate the association of Ye with macrophages in vivo.
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