000000839 001__ 839
000000839 005__ 20260421123241.0
000000839 0247_ $$2DOI$$a10.6083/M46D5R0T
000000839 037__ $$aETD
000000839 245__ $$aHow does salmonella evade the adaptive immune system?
000000839 260__ $$bOregon Health and Science University
000000839 269__ $$a2007
000000839 336__ $$aThesis
000000839 502__ $$bM.S.
000000839 502__ $$gMolecular Microbiology &amp; Immunology (sunsetting)
000000839 520__ $$aSalmonella enterica serotype Typhimurium is a Gram-negative facultative intracellular bacterium that causes a typhoid-like disease in mice. Salmonella invades the gut epithelium and establishes a systemic infection via invasion of phagocytes and replication within the Sa/monel/a-containing vacuole (SCV). Salmonella's gene expression is a response to its environment and allows the bacterium to avoid macrophage killing and to establish persistence. Our understanding of the mechanisms and virulence factors necessary for Salmonella to invade and initiate infection are far better understood than those required for thwarting the adaptive immune response, preventing clearance and establishing a long-term infection. It was the aim of this study to identify novel genes required in the evasion of the adaptive immune response. To identify Salmonella genes responsible for evading the adaptive immune response, we performed a microarray-based negative selection screen. Using a mutagenesis library, we infected RAG- mice that are missing 8 cells and T cells, as well as RAG+ mice, and compared the presence of mutants from spleens recovered at days five, six and seven. Following transposon detection, labeling, hybridization, quantitation, normalization and iii analysis, we identified a group of candidates. Using an allelic exchange protocol we individually knocked out these genes and used the strains in a competitive index experiment testing for persistence. Using qRT-PCR, we quantified bacterial numbers throughout the course of infection for each mutant strain as compared to control. We identified two Salmonella factors that are likely to be involved in evading the adaptive immune response, granting the bacterium the ability to prevent its own clearance. Listed as coding for a putative outer membrane or exported protein (STM4242) and putative cytoplasmic protein (STM 111 0), these genes are good candidates for further analysis of function and mechanism.
000000839 540__ $$fCC BY
000000839 542__ $$fIn copyright - single owner
000000839 650__ $$aSalmonella Infections$$025685
000000839 650__ $$aMacrophages$$021733
000000839 650__ $$aAdaptive Immunity$$038677
000000839 650__ $$aMice$$036842
000000839 650__ $$aSalmonella$$025680
000000839 650__ $$aSalmonella enterica$$031869
000000839 650__ $$aAllergy and Immunology$$014456
000000839 691__ $$aSchool of Medicine$$041369
000000839 692__ $$aDepartment of Molecular Microbiology and Immunology$$041429
000000839 7001_ $$aSchon, Catherine$$uOregon Health and Science University$$041354
000000839 7201_ $$aHeffron, Fred$$uOregon Health and Science University$$041354$$7Personal$$eMentor
000000839 8564_ $$95273f722-b50b-481b-8b1f-4d9bd95b63e3$$s2020011$$uhttps://digitalcollections.ohsu.edu/record/839/files/842_etd.pdf$$ePublic$$2338b4b8e39700a7d8af89de1098ec045$$31
000000839 901__ $$a&lt;p&gt;These documents are archival records. They are retained for historical reference only. &lt;/p&gt;&lt;p&gt;&lt;b&gt;Need an accessible version? Use the ‘Get Accessible Copy’ link above.&lt;/b&gt;&lt;/p&gt;
000000839 905__ $$a/rest/prod/b5/64/4r/56/b5644r56z
000000839 909CO $$ooai:digitalcollections.ohsu.edu:839$$pstudent-work
000000839 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument
000000839 980__ $$aTheses and Dissertations