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Coordinated Regulation of Salmonella Virulence Genes by the BarA/SirA Two-Component System and the Csr Global Regulatory System

Lucas, Darren Edward
http://rave.ohiolink.edu/etdc/view?acc_num=osu1374087620

Abstract Details

2013, Doctor of Philosophy, Ohio State University, Microbiology.
Salmonella enterica is the leading cause of death from foodborne illness in the United States. The mechanisms of its virulence have been well studied but key details have remained elusive. Salmonella expresses a type 1 fimbriae when transiting through the distal small intestine which enables it to bind to mannosylated glycoproteins present on the surface of intestinal epithelial cells. This allows the bacterium to dock to the cell utilizing the Salmonella pathogenicity island 1 encoded type three secretion system (SPI1-T3SS). Upon docking, Salmonella injects effector proteins into the host cell interrupting host cell function. This leads to an actin rearrangement at the site where the bacterium is docked which causes the host cell to engulf the bacterium in a process termed macropinocytosis. These processes are regulated tightly to ensure optimal expression at the time of invasion. The BarA/SirA two-component system in coordination with the Csr system are responsible for the regulation of these virulence traits. BarA is a sensor kinase that monitors the environment for the appropriate signal to start the virulence cascade. Though the signal remains elusive it is hypothesized to be the short chain fatty acids formate and acetate which are found in the distal ileum. Upon sensing these signals BarA phosphorylates SirA, which in turn can activate iii its target genes. To date only two direct targets have been identified for SirA, the small RNA’s csrB and csrC. These small non-coding RNAs are the antagonists of the RNA binding protein CsrA. Typically CsrA binds its target transcripts and prevents translation by blocking the ribosome. Through our studies we have attempted to unravel the pathways by which SirA and CsrA regulate the SPI1-T3SS and type 1 fimbriae to lead to successful invasion of the host cell. We show here that SirA has no direct binding targets in either SPI1 or the fim operon. SirA regulates SPI1 in an indirect manner through the activation of csrB and csrC. These ncRNA’s sequester CsrA and in turn allow for the translation of its targets in SPI1 which we have determined to be hilD and invF. Additionally CsrA regulates expression of the fim operon by direct binding and repression of the fimA transcript and the fimZ transcript. The combination of these studies clarify some of the mysteries of SPI1 and type 1 fimbrial regulation and provide new insights into the ability of the Csr system to regulate virulence in Salmonella.
Brian Ahmer, Ph.D. (Advisor)
Larry Schlesinger, MD/Ph.D. (Committee Member)
John Gunn, Ph.D. (Committee Member)
Robert Munson, Ph.D. (Committee Member)
219 p.
Genetics; Microbiology
Salmonella, BarA, SirA, CsrA, Csr, Salmonella Pathogenicity Island, SPI1, Carbon Storage Regulatory System, Type 1 Fimbriae, Fim, Small RNA,

Recommended Citations

Citations

  • Lucas, D. E. (2013). Coordinated Regulation of Salmonella Virulence Genes by the BarA/SirA Two-Component System and the Csr Global Regulatory System [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1374087620

    APA Style (7th edition)

  • Lucas, Darren. Coordinated Regulation of Salmonella Virulence Genes by the BarA/SirA Two-Component System and the Csr Global Regulatory System. 2013. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1374087620.

    MLA Style (8th edition)

  • Lucas, Darren. "Coordinated Regulation of Salmonella Virulence Genes by the BarA/SirA Two-Component System and the Csr Global Regulatory System." Doctoral dissertation, Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1374087620

    Chicago Manual of Style (17th edition)

osu1374087620
1,051
© 2013, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.