Salmonella enterica, a major causative agent of gastrointestinal illness, exhibits a host-specific pattern of infection, with certain serovars predominantly infecting particular hosts. Extensive variation is observed at the Salmonella rfb locus, which makes up serovar-defining O-antigen. Unlike other pathogens, this diversity cannot be explained by selective pressure from the host immune system. Here, I implicate the O-antigen to the physiological basis for escape from protozoan predators. These predators have differential feeding preferences on Salmonella and may be responsible for maintaining O-antigen diversity, controlling which serovars are able to survive predation to potentially cause disease. I demonstrated that the O-antigen plays a strong role in mediating predator escape and uncovered a trade-off that may exist between O-antigen identity and chain length regulation in response to the dual selective pressures of evading host intestinal predators and successful interaction with the host immune system. To complete these experiments, I developed two new techniques: a) genetic manipulation of non-Typhimurium Salmonella and b) multicolor flow cytometry for assessment of microbes in natural, complex environments. These results link variation at virulence loci to environmental selective pressures other than the host immune system and provide an explanation for the role of the rfb locus in the fragmented speciation process in Salmonella.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-08092011-041207 |
| Date | 16 September 2011 |
| Creators | Butela, Kristen A |
| Contributors | Dr. Graham Hatfull, Dr. Susan Kalisz, Dr. Valerie Oke, Dr. Jeffrey Lawrence, Dr. James Carroll |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-08092011-041207/ |
| Rights | restricted, 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 University of Pittsburgh 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. |
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