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Regulation of gene and sRNA expression in Francisella by PmrA

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2014, Master of Science, Ohio State University, Microbiology.
Francisella tularensis is a CDC Tier 1 select agent and has weaponizable potential. There is currently no licensed vaccine available in the United States, although a live vaccine strain (LVS) has been used by the former USSR and in certain labs within the United States. A stand-out feature of F. tularensis is that it lacks any classically arranged two-component systems and has few transcriptional regulators in its genome, unlike most other Gram-negative organisms. PmrA has previously been identified as an orphan response regulator that, upon phosphorylation by KdpD, activates the Francisella pathogenicity island (FPI). This activation and coordination with other transcriptional factors influences expression of virulence factors. We therefore hypothesized that the limited number of transcriptional regulators encoded in the F. tularensis genome must play key roles in the physiology and pathogenesis of F. tularensis within host cells. We also hypothesized that because Hfq is necessary for full virulence and has been known to promote sRNA-mRNA interactions, that sRNAs must be present in this organism and are involved in diverse functions, including pathogenesis. Comparisons between wildtype and ΔpmrA mutant strains of F. novicida and LVS between different laboratories across the United States revealed unexpected phenotypic differences in gene regulation, intramacrophage survival and mouse virulence. Upon investigating the potential causes of these observed phenotypic differences, it was determined that the cause was not related to PmrA expression, promoter mutation or downstream gene transcription. It is possible that there is something inherently different between these different laboratory strains and this needs further investigation. Utilizing RNA-seq, we determined the genes and putative sRNAs regulated by PmrA in F. novicida wildtype (JSG1819) and ¿pmrA (JSG2845). 28 genes were identified as exhibiting a two-fold or greater change in expression (12 activated, 16 repressed), with the four genes directly downstream of pmrA confirmed to be PmrA-activated. Using sRNA-seq, a total of 98 new putative sRNAs were identified including previously in silico predicted sRNAs. These data represent foundational studies characterizing and understanding Francisella virulence gene regulation.
John Gunn, Ph.D. (Advisor)
Michael Ibba, Ph.D. (Committee Member)
Brian Ahmer, Ph.D. (Committee Member)
Daniel Wozniak, Ph.D. (Committee Member)
125 p.

Recommended Citations

Citations

  • Olds, D. E. (2014). Regulation of gene and sRNA expression in Francisella by PmrA [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1417609882

    APA Style (7th edition)

  • Olds, Dominique. Regulation of gene and sRNA expression in Francisella by PmrA. 2014. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1417609882.

    MLA Style (8th edition)

  • Olds, Dominique. "Regulation of gene and sRNA expression in Francisella by PmrA." Master's thesis, Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1417609882

    Chicago Manual of Style (17th edition)