ingest cdrApp 2018-03-15T15:29:24.033Z d591f2cd-3da7-4b31-9dd8-ee27dcb6a3ee modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-03-15T15:30:14.329Z Setting exclusive relation addDatastream MD_TECHNICAL fedoraAdmin 2018-03-15T15:30:25.269Z Adding technical metadata derived by FITS addDatastream MD_FULL_TEXT fedoraAdmin 2018-03-15T15:30:48.362Z Adding full text metadata extracted by Apache Tika modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-03-15T15:31:10.457Z Setting exclusive relation modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-05-18T13:13:02.869Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-11T08:56:54.489Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-18T05:02:50.931Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-16T18:10:51.109Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-27T14:01:33.456Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-10-12T05:08:40.762Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-03-21T15:00:49.553Z Katelyn Zulauf Author Department of Microbiology and Immunology School of Medicine The role of SecA2 protein export in the virulence of Mycobacterium tuberculosis In order to promote disease, Mycobacterium tuberculosis exports proteins outside of the bacterial cell into the host environment where the proteins can interfere with host defense mechanisms such as phagosome maturation. The SecA2 pathway is one system M. tuberculosis utilizes to export such proteins. SecA2 is a non-essential specialized SecA ATPase required for exporting a relatively small subset of proteins. The SecA2 pathway, although not essential for growth of M. tuberculosis in vitro, is required for virulence of M. tuberculosis. The requirement for SecA2 during infection suggests that SecA2 and its exported effectors play important roles in M. tuberculosis pathogenesis. Therefore, we set out to both identify M. tuberculosis proteins that are exported by the SecA2 pathway and identify functions of SecA2 in M. tuberculosis virulence. Using quantitative proteomics, we identified solute binding proteins and Mce proteins as two classes of proteins exported by SecA2 as well additional proteins of unknown function that may account for the role of SecA2 in virulence. We additionally investigated the function of the SecA2 pathway in phagosome maturation arrest which is critical for M. tuberculosis replication and pathogenesis, by identifying and investigating proteins exported by the SecA2 pathway that play essential roles in this process. Work presented in this dissertation shows that SecA2 exports two effectors of phagosome maturation arrest: SapM and PknG. We further show that the role of SecA2 in exporting these effectors contributes to phagosome maturation arrest and growth of M. tuberculosis in macrophages. Finally, to further elucidate the functions and mechanisms of the SecA2 export pathway of M. tuberculosis beyond phagosome maturation arrest, we utilized genome-wide genetic interaction mapping of secA2. Our results expand our understanding of the SecA2 pathway by identifying candidate substrates and components of the export machinery and by revealing roles for SecA2 in M. tuberculosis processes involving transporters, phosphate import, copper resistance, peptidoglycan synthesis, and lipid metabolism and homeostasis. Taken together, the findings presented in this dissertation have significantly advanced our understanding of the roles of the SecA2 export pathway in the virulence of M. tuberculosis. Winter 2017 2017 Microbiology Mycobacterium tuberculosis, pathogenesis, phagosome maturation, protein export, SecA2 eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Miriam Braunstein Thesis advisor Thomas Kawula Thesis advisor Peggy Cotter Thesis advisor William Goldman Thesis advisor Rita Tamayo Thesis advisor text Katelyn Zulauf Creator Department of Microbiology and Immunology School of Medicine The role of SecA2 protein export in the virulence of Mycobacterium tuberculosis In order to promote disease, Mycobacterium tuberculosis exports proteins outside of the bacterial cell into the host environment where the proteins can interfere with host defense mechanisms such as phagosome maturation. The SecA2 pathway is one system M. tuberculosis utilizes to export such proteins. SecA2 is a non-essential specialized SecA ATPase required for exporting a relatively small subset of proteins. The SecA2 pathway, although not essential for growth of M. tuberculosis in vitro, is required for virulence of M. tuberculosis. The requirement for SecA2 during infection suggests that SecA2 and its exported effectors play important roles in M. tuberculosis pathogenesis. Therefore, we set out to both identify M. tuberculosis proteins that are exported by the SecA2 pathway and identify functions of SecA2 in M. tuberculosis virulence. Using quantitative proteomics, we identified solute binding proteins and Mce proteins as two classes of proteins exported by SecA2 as well additional proteins of unknown function that may account for the role of SecA2 in virulence. We additionally investigated the function of the SecA2 pathway in phagosome maturation arrest which is critical for M. tuberculosis replication and pathogenesis, by identifying and investigating proteins exported by the SecA2 pathway that play essential roles in this process. Work presented in this dissertation shows that SecA2 exports two effectors of phagosome maturation arrest: SapM and PknG. We further show that the role of SecA2 in exporting these effectors contributes to phagosome maturation arrest and growth of M. tuberculosis in macrophages. Finally, to further elucidate the functions and mechanisms of the SecA2 export pathway of M. tuberculosis beyond phagosome maturation arrest, we utilized genome-wide genetic interaction mapping of secA2. Our results expand our understanding of the SecA2 pathway by identifying candidate substrates and components of the export machinery and by revealing roles for SecA2 in M. tuberculosis processes involving transporters, phosphate import, copper resistance, peptidoglycan synthesis, and lipid metabolism and homeostasis. Taken together, the findings presented in this dissertation have significantly advanced our understanding of the roles of the SecA2 export pathway in the virulence of M. tuberculosis. 2017-12 2017 Microbiology Mycobacterium tuberculosis, pathogenesis, phagosome maturation, protein export, SecA2 eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Miriam Braunstein Thesis advisor Thomas Kawula Thesis advisor Peggy Cotter Thesis advisor William Goldman Thesis advisor Rita Tamayo Thesis advisor text Katelyn Zulauf Creator Department of Microbiology and Immunology School of Medicine The role of SecA2 protein export in the virulence of Mycobacterium tuberculosis In order to promote disease, Mycobacterium tuberculosis exports proteins outside of the bacterial cell into the host environment where the proteins can interfere with host defense mechanisms such as phagosome maturation. The SecA2 pathway is one system M. tuberculosis utilizes to export such proteins. SecA2 is a non-essential specialized SecA ATPase required for exporting a relatively small subset of proteins. The SecA2 pathway, although not essential for growth of M. tuberculosis in vitro, is required for virulence of M. tuberculosis. The requirement for SecA2 during infection suggests that SecA2 and its exported effectors play important roles in M. tuberculosis pathogenesis. Therefore, we set out to both identify M. tuberculosis proteins that are exported by the SecA2 pathway and identify functions of SecA2 in M. tuberculosis virulence. Using quantitative proteomics, we identified solute binding proteins and Mce proteins as two classes of proteins exported by SecA2 as well additional proteins of unknown function that may account for the role of SecA2 in virulence. We additionally investigated the function of the SecA2 pathway in phagosome maturation arrest which is critical for M. tuberculosis replication and pathogenesis, by identifying and investigating proteins exported by the SecA2 pathway that play essential roles in this process. Work presented in this dissertation shows that SecA2 exports two effectors of phagosome maturation arrest: SapM and PknG. We further show that the role of SecA2 in exporting these effectors contributes to phagosome maturation arrest and growth of M. tuberculosis in macrophages. Finally, to further elucidate the functions and mechanisms of the SecA2 export pathway of M. tuberculosis beyond phagosome maturation arrest, we utilized genome-wide genetic interaction mapping of secA2. Our results expand our understanding of the SecA2 pathway by identifying candidate substrates and components of the export machinery and by revealing roles for SecA2 in M. tuberculosis processes involving transporters, phosphate import, copper resistance, peptidoglycan synthesis, and lipid metabolism and homeostasis. Taken together, the findings presented in this dissertation have significantly advanced our understanding of the roles of the SecA2 export pathway in the virulence of M. tuberculosis. 2017-12 2017 Microbiology Mycobacterium tuberculosis, pathogenesis, phagosome maturation, protein export, SecA2 eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Miriam Braunstein Thesis advisor Thomas Kawula Thesis advisor Peggy Cotter Thesis advisor William Goldman Thesis advisor Rita Tamayo Thesis advisor text Katelyn Zulauf Creator Department of Microbiology and Immunology School of Medicine The role of SecA2 protein export in the virulence of Mycobacterium tuberculosis In order to promote disease, Mycobacterium tuberculosis exports proteins outside of the bacterial cell into the host environment where the proteins can interfere with host defense mechanisms such as phagosome maturation. The SecA2 pathway is one system M. tuberculosis utilizes to export such proteins. SecA2 is a non-essential specialized SecA ATPase required for exporting a relatively small subset of proteins. The SecA2 pathway, although not essential for growth of M. tuberculosis in vitro, is required for virulence of M. tuberculosis. The requirement for SecA2 during infection suggests that SecA2 and its exported effectors play important roles in M. tuberculosis pathogenesis. Therefore, we set out to both identify M. tuberculosis proteins that are exported by the SecA2 pathway and identify functions of SecA2 in M. tuberculosis virulence. Using quantitative proteomics, we identified solute binding proteins and Mce proteins as two classes of proteins exported by SecA2 as well additional proteins of unknown function that may account for the role of SecA2 in virulence. We additionally investigated the function of the SecA2 pathway in phagosome maturation arrest which is critical for M. tuberculosis replication and pathogenesis, by identifying and investigating proteins exported by the SecA2 pathway that play essential roles in this process. Work presented in this dissertation shows that SecA2 exports two effectors of phagosome maturation arrest: SapM and PknG. We further show that the role of SecA2 in exporting these effectors contributes to phagosome maturation arrest and growth of M. tuberculosis in macrophages. Finally, to further elucidate the functions and mechanisms of the SecA2 export pathway of M. tuberculosis beyond phagosome maturation arrest, we utilized genome-wide genetic interaction mapping of secA2. Our results expand our understanding of the SecA2 pathway by identifying candidate substrates and components of the export machinery and by revealing roles for SecA2 in M. tuberculosis processes involving transporters, phosphate import, copper resistance, peptidoglycan synthesis, and lipid metabolism and homeostasis. Taken together, the findings presented in this dissertation have significantly advanced our understanding of the roles of the SecA2 export pathway in the virulence of M. tuberculosis. 2017-12 2017 Microbiology Mycobacterium tuberculosis, pathogenesis, phagosome maturation, protein export, SecA2 eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Miriam Braunstein Thesis advisor Thomas Kawula Thesis advisor Peggy Cotter Thesis advisor William Goldman Thesis advisor Rita Tamayo Thesis advisor text Katelyn Zulauf Creator Department of Microbiology and Immunology School of Medicine The role of SecA2 protein export in the virulence of Mycobacterium tuberculosis In order to promote disease, Mycobacterium tuberculosis exports proteins outside of the bacterial cell into the host environment where the proteins can interfere with host defense mechanisms such as phagosome maturation. The SecA2 pathway is one system M. tuberculosis utilizes to export such proteins. SecA2 is a non-essential specialized SecA ATPase required for exporting a relatively small subset of proteins. The SecA2 pathway, although not essential for growth of M. tuberculosis in vitro, is required for virulence of M. tuberculosis. The requirement for SecA2 during infection suggests that SecA2 and its exported effectors play important roles in M. tuberculosis pathogenesis. Therefore, we set out to both identify M. tuberculosis proteins that are exported by the SecA2 pathway and identify functions of SecA2 in M. tuberculosis virulence. Using quantitative proteomics, we identified solute binding proteins and Mce proteins as two classes of proteins exported by SecA2 as well additional proteins of unknown function that may account for the role of SecA2 in virulence. We additionally investigated the function of the SecA2 pathway in phagosome maturation arrest which is critical for M. tuberculosis replication and pathogenesis, by identifying and investigating proteins exported by the SecA2 pathway that play essential roles in this process. Work presented in this dissertation shows that SecA2 exports two effectors of phagosome maturation arrest: SapM and PknG. We further show that the role of SecA2 in exporting these effectors contributes to phagosome maturation arrest and growth of M. tuberculosis in macrophages. Finally, to further elucidate the functions and mechanisms of the SecA2 export pathway of M. tuberculosis beyond phagosome maturation arrest, we utilized genome-wide genetic interaction mapping of secA2. Our results expand our understanding of the SecA2 pathway by identifying candidate substrates and components of the export machinery and by revealing roles for SecA2 in M. tuberculosis processes involving transporters, phosphate import, copper resistance, peptidoglycan synthesis, and lipid metabolism and homeostasis. Taken together, the findings presented in this dissertation have significantly advanced our understanding of the roles of the SecA2 export pathway in the virulence of M. tuberculosis. 2017-12 2017 Microbiology Mycobacterium tuberculosis, pathogenesis, phagosome maturation, protein export, SecA2 eng Doctor of Philosophy Dissertation Microbiology and Immunology Miriam Braunstein Thesis advisor Thomas Kawula Thesis advisor Peggy Cotter Thesis advisor William Goldman Thesis advisor Rita Tamayo Thesis advisor text University of North Carolina at Chapel Hill Degree granting institution Katelyn Zulauf Creator Department of Microbiology and Immunology School of Medicine The role of SecA2 protein export in the virulence of Mycobacterium tuberculosis In order to promote disease, Mycobacterium tuberculosis exports proteins outside of the bacterial cell into the host environment where the proteins can interfere with host defense mechanisms such as phagosome maturation. The SecA2 pathway is one system M. tuberculosis utilizes to export such proteins. SecA2 is a non-essential specialized SecA ATPase required for exporting a relatively small subset of proteins. The SecA2 pathway, although not essential for growth of M. tuberculosis in vitro, is required for virulence of M. tuberculosis. The requirement for SecA2 during infection suggests that SecA2 and its exported effectors play important roles in M. tuberculosis pathogenesis. Therefore, we set out to both identify M. tuberculosis proteins that are exported by the SecA2 pathway and identify functions of SecA2 in M. tuberculosis virulence. Using quantitative proteomics, we identified solute binding proteins and Mce proteins as two classes of proteins exported by SecA2 as well additional proteins of unknown function that may account for the role of SecA2 in virulence. We additionally investigated the function of the SecA2 pathway in phagosome maturation arrest which is critical for M. tuberculosis replication and pathogenesis, by identifying and investigating proteins exported by the SecA2 pathway that play essential roles in this process. Work presented in this dissertation shows that SecA2 exports two effectors of phagosome maturation arrest: SapM and PknG. We further show that the role of SecA2 in exporting these effectors contributes to phagosome maturation arrest and growth of M. tuberculosis in macrophages. Finally, to further elucidate the functions and mechanisms of the SecA2 export pathway of M. tuberculosis beyond phagosome maturation arrest, we utilized genome-wide genetic interaction mapping of secA2. Our results expand our understanding of the SecA2 pathway by identifying candidate substrates and components of the export machinery and by revealing roles for SecA2 in M. tuberculosis processes involving transporters, phosphate import, copper resistance, peptidoglycan synthesis, and lipid metabolism and homeostasis. Taken together, the findings presented in this dissertation have significantly advanced our understanding of the roles of the SecA2 export pathway in the virulence of M. tuberculosis. 2017-12 2017 Microbiology Mycobacterium tuberculosis; pathogenesis; phagosome maturation; protein export; SecA2 eng Doctor of Philosophy Dissertation Microbiology and Immunology Miriam Braunstein Thesis advisor Thomas Kawula Thesis advisor Peggy Cotter Thesis advisor William Goldman Thesis advisor Rita Tamayo Thesis advisor text University of North Carolina at Chapel Hill Degree granting institution Katelyn Zulauf Creator Department of Microbiology and Immunology School of Medicine The role of SecA2 protein export in the virulence of Mycobacterium tuberculosis In order to promote disease, Mycobacterium tuberculosis exports proteins outside of the bacterial cell into the host environment where the proteins can interfere with host defense mechanisms such as phagosome maturation. The SecA2 pathway is one system M. tuberculosis utilizes to export such proteins. SecA2 is a non-essential specialized SecA ATPase required for exporting a relatively small subset of proteins. The SecA2 pathway, although not essential for growth of M. tuberculosis in vitro, is required for virulence of M. tuberculosis. The requirement for SecA2 during infection suggests that SecA2 and its exported effectors play important roles in M. tuberculosis pathogenesis. Therefore, we set out to both identify M. tuberculosis proteins that are exported by the SecA2 pathway and identify functions of SecA2 in M. tuberculosis virulence. Using quantitative proteomics, we identified solute binding proteins and Mce proteins as two classes of proteins exported by SecA2 as well additional proteins of unknown function that may account for the role of SecA2 in virulence. We additionally investigated the function of the SecA2 pathway in phagosome maturation arrest which is critical for M. tuberculosis replication and pathogenesis, by identifying and investigating proteins exported by the SecA2 pathway that play essential roles in this process. Work presented in this dissertation shows that SecA2 exports two effectors of phagosome maturation arrest: SapM and PknG. We further show that the role of SecA2 in exporting these effectors contributes to phagosome maturation arrest and growth of M. tuberculosis in macrophages. Finally, to further elucidate the functions and mechanisms of the SecA2 export pathway of M. tuberculosis beyond phagosome maturation arrest, we utilized genome-wide genetic interaction mapping of secA2. Our results expand our understanding of the SecA2 pathway by identifying candidate substrates and components of the export machinery and by revealing roles for SecA2 in M. tuberculosis processes involving transporters, phosphate import, copper resistance, peptidoglycan synthesis, and lipid metabolism and homeostasis. Taken together, the findings presented in this dissertation have significantly advanced our understanding of the roles of the SecA2 export pathway in the virulence of M. tuberculosis. 2017-12 2017 Microbiology Mycobacterium tuberculosis, pathogenesis, phagosome maturation, protein export, SecA2 eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Miriam Braunstein Thesis advisor Thomas Kawula Thesis advisor Peggy Cotter Thesis advisor William Goldman Thesis advisor Rita Tamayo Thesis advisor text Katelyn Zulauf Creator Department of Microbiology and Immunology School of Medicine In order to promote disease, Mycobacterium tuberculosis exports proteins outside of the bacterial cell into the host environment where the proteins can interfere with host defense mechanisms such as phagosome maturation. The SecA2 pathway is one system M. tuberculosis utilizes to export such proteins. SecA2 is a non-essential specialized SecA ATPase required for exporting a relatively small subset of proteins. The SecA2 pathway, although not essential for growth of M. tuberculosis in vitro, is required for virulence of M. tuberculosis. The requirement for SecA2 during infection suggests that SecA2 and its exported effectors play important roles in M. tuberculosis pathogenesis. Therefore, we set out to both identify M. tuberculosis proteins that are exported by the SecA2 pathway and identify functions of SecA2 in M. tuberculosis virulence. Using quantitative proteomics, we identified solute binding proteins and Mce proteins as two classes of proteins exported by SecA2 as well additional proteins of unknown function that may account for the role of SecA2 in virulence. We additionally investigated the function of the SecA2 pathway in phagosome maturation arrest which is critical for M. tuberculosis replication and pathogenesis, by identifying and investigating proteins exported by the SecA2 pathway that play essential roles in this process. Work presented in this dissertation shows that SecA2 exports two effectors of phagosome maturation arrest: SapM and PknG. We further show that the role of SecA2 in exporting these effectors contributes to phagosome maturation arrest and growth of M. tuberculosis in macrophages. Finally, to further elucidate the functions and mechanisms of the SecA2 export pathway of M. tuberculosis beyond phagosome maturation arrest, we utilized genome-wide genetic interaction mapping of secA2. Our results expand our understanding of the SecA2 pathway by identifying candidate substrates and components of the export machinery and by revealing roles for SecA2 in M. tuberculosis processes involving transporters, phosphate import, copper resistance, peptidoglycan synthesis, and lipid metabolism and homeostasis. Taken together, the findings presented in this dissertation have significantly advanced our understanding of the roles of the SecA2 export pathway in the virulence of M. tuberculosis. 2017-12 2017 Microbiology Mycobacterium tuberculosis; pathogenesis; phagosome maturation; protein export; SecA2 eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Miriam Braunstein Thesis advisor Thomas Kawula Thesis advisor Peggy Cotter Thesis advisor William Goldman Thesis advisor Rita Tamayo Thesis advisor text Zulauf_unc_0153D_17437.pdf uuid:8da5edad-6da6-43d3-a504-0d6655bdc3c0 2019-12-31T00:00:00 2017-11-28T19:50:34Z proquest application/pdf 6973550