Date of Award

5-2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biological Science

Committee Chair

Daoguo Zhou

Committee Member 1

Zhao-Qing Luo

Committee Member 2

Henry C. Chang

Committee Member 3

Seema Mattoo

Abstract

Salmonella pathogenesis primarily involves invasion of host cells followed by modulation of the intracellular environment for survival and replication. While tremendous progress has been made toward understanding the pathogenesis, the picture is far from complete. In an effort to characterize the role of small RNAs (sRNAs) in Salmonella pathogenesis, we identified a previously undefined small protein YshB as a positive regulator for intracellular bacterial survival and virulence. Essentially, we were able to show YshB was important for survival within macrophages and contributed significantly in mouse virulence. Further, when induced within the bacteria, YshB would lower the invasion efficiency. Notably, yshB expression was found to up-regulate when the bacteria were inside macrophage cells. Moreover, we demonstrate that YshB mediates upregulation of PhoP, a key modulator of Salmonella virulence. We therefore propose a scenario where the induction of YshB mimics the intracellular phase and therefore triggers a down-regulation of the invasion machinery. Interestingly, during the process of elucidating the mechanism of regulation mediated by this small protein, we came across a link between bacterial pathogenesis and fatty acid oxidation pathway. In particular, we found that FadB, an enzyme involved in breakdown of long chain fatty acids was upregulated in the Salmonella cells with induced YshB. FadB was previously implicated to be one of the in vivo induced (ivi) genes, which lead us to speculate that this gene might be important to maintain intracellular survival of Salmonella. We were able to demonstrate that the fadB knockout mutants were indeed compromised in their intracellular life cycle. The upregulation of PhoP and FadB in the YshB induced cells might therefore trigger the spatio-temporal switch from invasion-competent phase of infection to a survival-competent phase. Based on the results we gathered, we therefore postulate a role for this small protein as a molecular liaison to mediate a cross-talk between the invasion competent extracellular and the survival competent intracellular phase of Salmonella.

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