Extensive genetic variability at particular loci is observed among many bacteria because alleles confer higher fitness advantages under certain situations. Extensive diversity is observed at the Salmonella rfb locus, encoding enzymes responsible for synthesis of the O-antigen polysaccharide. Historically, diversity at the rfb locus was thought to be caused by selective pressures from the immune system and maintained by frequency dependent selection (FDS). This hypothesis works well for pathogens like Haemophilus influenzae and Neisseria meningitis, which alter their O-antigens during the course of an infection. In contrast, Salmonella does not alter its O-antigen. More importantly, Salmonella shows host-serovar specificity, whereby strains bearing certain O-antigens cause disease primarily in specific hosts; this is inconsistent with FDS. Alternatively, selective pressure may originate from the host intestinal environment itself, wherein diversifying selection (DS) mediated by protozoan predation allows for the continued maintenance of rfb diversity and the survival of Salmonella. To test if predation may be a selective pressure influencing O-antigen diversity, amoebae were isolated from separate intestinal environments and shown that these amoebae recognize antigenically diverse Salmonella with different efficiencies. More importantly, it was demonstrated that feeding preferences are upheld when Salmonella differ only by their O-antigen. Thus, protozoan predation may be the selective pressure influencing O-antigen diversity. For extensive genetic diversity to be maintained by DS, a particular O-antigen should confer a higher fitness in a certain environment. To test this hypothesis, amoebae were isolated from the intestines of fish, tadpoles, lizards, and turtles and their feeding preferences were determined. As expected, related amoeba from the same host share preferences. Strikingly, unrelated amoebae from the same intestinal environment also had significantly similar feeding preferences, and related amoebae isolated from different environments showed no similarity in prey choice. This demonstrates that amoebae from an environment share feeding preferences. In concert, O-antigen variability may result from selective pressures of predation and subsequently may be maintained by DS whereby a certain O-antigen confers a higher fitness advantage depending on its residing environment. This makes sense of the serovar-host specificity and the clonality of O-antigens among Salmonella that were not explained by previous hypotheses.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-12132006-112138 |
| Date | 13 December 2006 |
| Creators | Wildschutte, Hans K |
| Contributors | Graham Hatfull, Charles Walsh, JoAnne Flynn, Jeffrey Lawrence, Timothy Mietzner |
| 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-12132006-112138/ |
| Rights | unrestricted, 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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