Genetic and environmental regulation of virulence genes in Salmonella enterica serovar Typhimurium.

The purpose of this research has been to assess the effect of the genetic regulator, CsrA, and environmental conditions on the expression of virulence genes in Salmonella enterica serovar Typhimurium. CsrA is an RNA binding protein that alters messenger RNA stability in E. coli and regulates virulence genes located on the Salmonella pathogenicity island 1 (SPI-1). This work demonstrates that CsrA in S. typhimurium like its counterpart in E. coli regulates expression of genes required for flagellar synthesis and suggests a role for CsrA in the positive regulation of utilization of propanediol and ethanolamine, vitamin B12 synthesis, and expression of maltoporin, which transports maltose and maltodextrins across the bacterial cell membrane. Propanediol, ethanolamine, and maltodextrins are byproducts of digestion likely present in the intestinal tract. Vitamin B12 is required for utilization of propanediol and ethanolamine. The sensor kinase BarA and its response regulator SirA control levels of CsrA indirectly through the expression of an untranslated RNA CsrB, which binds CsrA. SirA regulates expression of Salmonella virulence genes and is required for Salmonella enteropathogenesis. BarA and SirA have the opposite effects on propanediol and ethanolamine utilization, and vitamin B12 synthesis as CsrA, thus supporting the model of indirect regulation of CsrA by BarA/SirA. In addition, the short chain fatty acids (SCFA) acetate, propionate, and butyrate are present in the ileum and colon at differing total concentrations and relative percentages. SCFAs representing the ileum and acetate alone are able to restore SPI-1 invasion gene expression to a barA mutant but not to a sirA mutant. Additionally, ileal SCFAs increase the expression of SPI-1 virulence genes required for invasion of epithelial cells and increase the expression of genes required for survival within epithelial cells and macrophages. SCFAs representing the colon decrease expression of genes required for epithelial cell invasion and decrease the expression of genes required for flagellar synthesis and maltose transport while increasing the expression of genes required for glycerol and propanediol metabolism.

Author dc:creator

• Lawhon, Sara Dyann

Advisors dc:contributor.advisor

• Craig Altier, Committee Co-Chair
• Paul Orndorff, Committee Co-Chair
• Steve Libby, Committee Member
• Gerry Luginbuhl, Committee Member

• short chain fatty acids
• SPI-1
• SPI-2
• invasion
• flagella
• BarA
• SirA
• virulence
• maltose
• ethanolamine
• propanediol
• vitamin B12
• acetate
• CsrA
• CsrB

Statement dc:rights

• I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to NC State University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.

Dc Identifier Other

etd-11142002-195208

OAI record oai:identifier

https://repository.lib.ncsu.edu/server/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Arepository.lib.ncsu.edu%3A1840.16%2F3361