Dissertation
POSTTRANSCRIPTIONAL REGULATORY MECHANISMS OF THE YERSINIA PESTIS RNA-BINDING PROTEIN, CSRA, IN STIMULATING CYCLIC-DI-GMP SNYTHESIS AND FOREGUT BIOFILM-MEDIATED BLOCKAGE TRANSMISSION FROM FLEAS
Washington State University
Doctor of Philosophy (PhD), Washington State University
01/2021
DOI:
https://doi.org/10.7273/000002406
Handle:
https://hdl.handle.net/2376/123989
Abstract
Plague-causing, Yersinia pestis, produces a regurgitative, biofilm-mediated blockage infection in fleas which facilitates the primary transmission route between mammalian hosts. It is well studied how the major component of Y. pestis biofilm, the extracellular polysaccharide (EPS) poly-N-acetylglucosamine, is synthesized and exported by protein products of the hemin storage operon hmsHFRS and induced by the chemical messenger, cyclic-di-GMP (c-di-GMP). However, nutrient signals within the flea gut that regulate synthesis and degradation of c-di-GMP are not well understood. In separate studies, it was shown that csrA encoding the highly conserved RNA-binding protein, the carbon storage regulator protein (CsrA), promotes Y. pestis biofilm formation and is highly upregulated in Y. pestis infected fleas that had developed a biofilm-mediated blockage infection. In many Gammaproteobacteria, CsrA is involved with coordinating levels of c-di-GMP and EPS production in response to the bacteria’s nutritional status. In this dissertation work, we sought out to do determine 1) whether CsrA could regulate biofilm formation in response to flea relevant sugars, 2) the mechanism of how CsrA regulates biofilm formation, and 3) if CsrA has a role in the physiologically relevant context of in vivo biofilm-mediated blockage infection. We show that CsrA is critical for stimulating c-di-GMP synthesis to increase EPS levels coincident with alternative carbon metabolism, specifically of flea relevant sugars, ribose and galactose. Additionally, we show that CsrA posttranscriptional directly controls of hmsE and hfq mRNAs at the posttranslational level to indirectly increases c-di-GMP synthesis activity through HmsD, required for the formation of biofilm-mediated infection in fleas, and HmsT, required for in vitro biofilm formation. Lastly, we show that CsrA is required for efficient formation of biofilm-mediated blockage infection in fleas. Noteworthy is that the Y. pestis-flea interaction represents a unique biologically relevant, in vivo perspective on the role of CsrA in biofilm regulation.
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Details
- Title
- POSTTRANSCRIPTIONAL REGULATORY MECHANISMS OF THE YERSINIA PESTIS RNA-BINDING PROTEIN, CSRA, IN STIMULATING CYCLIC-DI-GMP SNYTHESIS AND FOREGUT BIOFILM-MEDIATED BLOCKAGE TRANSMISSION FROM FLEAS
- Creators
- Amelia Rose Silva
- Contributors
- Viveka Vadyvaloo (Advisor)Troy Bankhead (Committee Member)Leigh Knodler (Committee Member)Susan Noh (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Veterinary Medicine, College of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 125
- Identifiers
- 99900606752701842
- Language
- English
- Resource Type
- Dissertation