{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/10400"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/10400","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Characterization of Virulence Mechanisms in Vibrio parahaemolyticus","abstract":"Pages xvi-xix are misnumbered as pages vi-ix.","abstract_html":"Pages xvi-xix are misnumbered as pages vi-ix.","abstract_has_math":false,"creators":["Lafrance, Alexander Ethan"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Hendrixson, David R.","Alto, Neal","Tomchick, Diana R.","Orth, Kim"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-09-20T22:10:16Z","date_published":"2024-09-20T22:10:16Z","updated_at":"2026-07-24T05:52:36Z","subjects":["Bacterial Infections","Bacterial Proteins","Cholesterol","Escherichia coli Proteins","Fatty Acids","Lipase","Uropathogenic Escherichia coli","Vibrio parahaemolyticus"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["1456721232"],"render_values":[{"text":"1456721232","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/10400","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Hendrixson, David R.","Alto, Neal","Tomchick, Diana R.","Orth, Kim"]},{"key":"dc:creator","label":"Author","values":["Lafrance, Alexander Ethan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2024-09-20T22:10:16Z","2022-08","August 2022"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Bacterial Infections","Bacterial Proteins","Cholesterol","Escherichia coli Proteins","Fatty Acids","Lipase","Uropathogenic Escherichia coli","Vibrio parahaemolyticus"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/10400","1456721232"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Pages xvi-xix are misnumbered as pages vi-ix.","Vibrio parahaemolyticus (V. parahaemolyticus) is a Gram-negative, halophilic bacterium found in estuarine and marine environments worldwide, and is a leading cause of foodborne illness. The V. parahaemolyticus life cycle is facilitated by a broad array of virulence factors, including two type three secretion systems (T3SS). Within the T3SS1 effector repertoire, VopR induces cytoskeletal collapse, cell rounding, and actin localization to the host cell periphery, but its catalytic activity, substrate, and cognate chaperone remained uncharacterized. Herein, we investigated the catalytic mechanism of VopR, evaluated potential substrates through structural analyses and biochemical assays, and identified VP1684 as the cognate chaperone for VopR. V. parahaemolyticus also mediates an intracellular infection via the T3SS2. The T3SS2 effector VopC promotes host invasion by deamidating small host Rho GTPases. Rho GTPase deamidation is a highly conserved invasion strategy in Gram-negative bacteria, including the human pathogen uropathogenic Escherichia coli (UPEC). UPEC secretes a Rho GTPase deamidating toxin CNF1, a VopC homologue, that enters the host via endocytosis. Herein we determined that CNF1 can complement VopC activity in promoting V. parahaemolyticus invasion, but leaves many internalized bacteria confined to endosomes. We also investigated the mechanism by which V. parahaemolyticus exits the host cell, and found that a type two secretion system (T2SS)-secreted lipase VPA0226 was necessary for bacterial egress, marking the successful completion of the infection process. Finally, we utilized in silico analyses and a transposon mutagenesis screen to identify novel putative virulence factors in and outside the V. parahaemolyticus T3SS effector repertoire, and uncovered a putative GABA antiporter with a significant effect on bacterial proliferation, and possibly pH regulation. Cumulatively, these studies highlight the diversity of the virulence factors and complex networks involving an interdependency between these factors in a clinically relevant human pathogen."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Characterization of Virulence Mechanisms in Vibrio parahaemolyticus"]}]}],"canonical_facts":{"dc:contributor":["Hendrixson, David R.","Alto, Neal","Tomchick, Diana R.","Orth, Kim"],"dc:creator":["Lafrance, Alexander Ethan"],"dc:date":["2024-09-20T22:10:16Z","2022-08","August 2022"],"dc:description":["Pages xvi-xix are misnumbered as pages vi-ix.","Vibrio parahaemolyticus (V. parahaemolyticus) is a Gram-negative, halophilic bacterium found in estuarine and marine environments worldwide, and is a leading cause of foodborne illness. The V. parahaemolyticus life cycle is facilitated by a broad array of virulence factors, including two type three secretion systems (T3SS). Within the T3SS1 effector repertoire, VopR induces cytoskeletal collapse, cell rounding, and actin localization to the host cell periphery, but its catalytic activity, substrate, and cognate chaperone remained uncharacterized. Herein, we investigated the catalytic mechanism of VopR, evaluated potential substrates through structural analyses and biochemical assays, and identified VP1684 as the cognate chaperone for VopR. V. parahaemolyticus also mediates an intracellular infection via the T3SS2. The T3SS2 effector VopC promotes host invasion by deamidating small host Rho GTPases. Rho GTPase deamidation is a highly conserved invasion strategy in Gram-negative bacteria, including the human pathogen uropathogenic Escherichia coli (UPEC). UPEC secretes a Rho GTPase deamidating toxin CNF1, a VopC homologue, that enters the host via endocytosis. Herein we determined that CNF1 can complement VopC activity in promoting V. parahaemolyticus invasion, but leaves many internalized bacteria confined to endosomes. We also investigated the mechanism by which V. parahaemolyticus exits the host cell, and found that a type two secretion system (T2SS)-secreted lipase VPA0226 was necessary for bacterial egress, marking the successful completion of the infection process. Finally, we utilized in silico analyses and a transposon mutagenesis screen to identify novel putative virulence factors in and outside the V. parahaemolyticus T3SS effector repertoire, and uncovered a putative GABA antiporter with a significant effect on bacterial proliferation, and possibly pH regulation. Cumulatively, these studies highlight the diversity of the virulence factors and complex networks involving an interdependency between these factors in a clinically relevant human pathogen."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/10400","1456721232"],"dc:language":["en"],"dc:subject":["Bacterial Infections","Bacterial Proteins","Cholesterol","Escherichia coli Proteins","Fatty Acids","Lipase","Uropathogenic Escherichia coli","Vibrio parahaemolyticus"],"dc:title":["Characterization of Virulence Mechanisms in Vibrio parahaemolyticus"],"dc:type":["Thesis","text"]},"updated_at":"2026-07-24T05:52:36Z"}