ingest cdrApp 2017-08-15T22:44:35.232Z d91e81c8-5a8a-4e8a-976c-cad4e396e5ee modifyDatastreamByValue RELS-EXT fedoraAdmin 2017-08-15T22:45:34.237Z Setting exclusive relation modifyDatastreamByValue RELS-EXT fedoraAdmin 2017-08-15T22:45:43.504Z Setting exclusive relation addDatastream MD_TECHNICAL fedoraAdmin 2017-08-15T22:45:57.561Z Adding technical metadata derived by FITS modifyDatastreamByValue RELS-EXT fedoraAdmin 2017-08-15T22:46:15.281Z Setting exclusive relation addDatastream MD_FULL_TEXT fedoraAdmin 2017-08-15T22:46:25.442Z Adding full text metadata extracted by Apache Tika modifyDatastreamByValue RELS-EXT fedoraAdmin 2017-08-15T22:46:43.890Z Setting exclusive relation modifyDatastreamByValue RELS-EXT cdrApp 2017-08-22T13:57:16.428Z Setting exclusive relation modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-01-25T08:19:31.433Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-01-27T08:38:28.394Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-03-14T05:11:45.066Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-05-17T16:46:28.429Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-11T03:38:54.211Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-17T23:56:54.927Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-15T20:05:35.286Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-21T20:23:00.722Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-26T23:42:18.738Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-10-12T00:16:59.337Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-03-20T18:17:44.453Z Michelle Palacios Author Department of Microbiology and Immunology School of Medicine Identification of conserved Klebsiella pneumoniae virulence factors Klebsiella pneumoniae is an urgent threat to public health due to nosocomial outbreaks of multi-drug resistant strains and the emergence of hypervirulent community acquired infections. Only in recent years have we gained a better understanding of the population structure of emergent clones and insight on the high level of strain-to-strain genomic variation K. pneumoniae strains display. While capsule and siderophores are considered primary virulence factors of K. pneumoniae, the number of siderophore types encoded and the capsule type can vary significantly from strain-to-strain. Thus, identifying highly conserved virulence mechanisms is essential for therapeutic development. This work focused on the use of a murine pneumonia model of infection and a sputum-derived isolate of K. pneumoniae to identify previously uncharacterized virulence factors. In Chapter 2, we describe how a serendipitous mutation led us to identify the periplasmic importer of enterobactin, FepB, as being a unique contributor to virulence. Interestingly, the contribution of FepB to virulence was greater than the contribution of enterobactin to virulence suggesting a greater role than enterobactin transport. Given that FepB is present in other pathogenic Enterobacteriaceae, our findings may be applicable to other pathogens. In an attempt to expand our knowledge of the repertoire of K. pneumoniae virulence factors, we also conducted an in vivo screen of the contribution of MarR-like transcriptional regulators to virulence in Chapter 3. We identified two previously unidentified regulators of virulence in K. pneumoniae, and have named these KvrA and KvrB. KvrA and KvrB are highly conserved across K. pneumoniae species. Both regulators regulated capsule expression and production, and this regulation appeared to be conserved in an isolate of a different capsule type. Interestingly, while KvrA and KvrB regulate capsule in a similar fashion, the in vivo kinetics of infection of the kvrA and kvrB mutants were quite distinct suggesting that the regulons of KvrA and KvrB are unique from each other. Because our studies focused on highly conserved virulence factors, our work has implications for the development of novel anti-Klebsiella therapeutics. Summer 2017 2017 Microbiology Biology Molecular biology bacteria, infection, pathogenesis, regulation, siderophores, virulence eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Virginia Miller Thesis advisor Thomas Kawula Thesis advisor Rob Maile Thesis advisor Bruce Cairns Thesis advisor Peggy Cotter Thesis advisor Janella Arthur Thesis advisor text Michelle Palacios Creator Department of Microbiology and Immunology School of Medicine Identification of conserved Klebsiella pneumoniae virulence factors Klebsiella pneumoniae is an urgent threat to public health due to nosocomial outbreaks of multi-drug resistant strains and the emergence of hypervirulent community acquired infections. Only in recent years have we gained a better understanding of the population structure of emergent clones and insight on the high level of strain-to-strain genomic variation K. pneumoniae strains display. While capsule and siderophores are considered primary virulence factors of K. pneumoniae, the number of siderophore types encoded and the capsule type can vary significantly from strain-to-strain. Thus, identifying highly conserved virulence mechanisms is essential for therapeutic development. This work focused on the use of a murine pneumonia model of infection and a sputum-derived isolate of K. pneumoniae to identify previously uncharacterized virulence factors. In Chapter 2, we describe how a serendipitous mutation led us to identify the periplasmic importer of enterobactin, FepB, as being a unique contributor to virulence. Interestingly, the contribution of FepB to virulence was greater than the contribution of enterobactin to virulence suggesting a greater role than enterobactin transport. Given that FepB is present in other pathogenic Enterobacteriaceae, our findings may be applicable to other pathogens. In an attempt to expand our knowledge of the repertoire of K. pneumoniae virulence factors, we also conducted an in vivo screen of the contribution of MarR-like transcriptional regulators to virulence in Chapter 3. We identified two previously unidentified regulators of virulence in K. pneumoniae, and have named these KvrA and KvrB. KvrA and KvrB are highly conserved across K. pneumoniae species. Both regulators regulated capsule expression and production, and this regulation appeared to be conserved in an isolate of a different capsule type. Interestingly, while KvrA and KvrB regulate capsule in a similar fashion, the in vivo kinetics of infection of the kvrA and kvrB mutants were quite distinct suggesting that the regulons of KvrA and KvrB are unique from each other. Because our studies focused on highly conserved virulence factors, our work has implications for the development of novel anti-Klebsiella therapeutics. Summer 2017 2017 Microbiology Biology Molecular biology bacteria, infection, pathogenesis, regulation, siderophores, virulence eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Virginia Miller Thesis advisor Thomas Kawula Thesis advisor Rob Maile Thesis advisor Bruce Cairns Thesis advisor Peggy Cotter Thesis advisor Janella Arthur Thesis advisor text Michelle Palacios Creator Department of Microbiology and Immunology School of Medicine Identification of conserved Klebsiella pneumoniae virulence factors Klebsiella pneumoniae is an urgent threat to public health due to nosocomial outbreaks of multi-drug resistant strains and the emergence of hypervirulent community acquired infections. Only in recent years have we gained a better understanding of the population structure of emergent clones and insight on the high level of strain-to-strain genomic variation K. pneumoniae strains display. While capsule and siderophores are considered primary virulence factors of K. pneumoniae, the number of siderophore types encoded and the capsule type can vary significantly from strain-to-strain. Thus, identifying highly conserved virulence mechanisms is essential for therapeutic development. This work focused on the use of a murine pneumonia model of infection and a sputum-derived isolate of K. pneumoniae to identify previously uncharacterized virulence factors. In Chapter 2, we describe how a serendipitous mutation led us to identify the periplasmic importer of enterobactin, FepB, as being a unique contributor to virulence. Interestingly, the contribution of FepB to virulence was greater than the contribution of enterobactin to virulence suggesting a greater role than enterobactin transport. Given that FepB is present in other pathogenic Enterobacteriaceae, our findings may be applicable to other pathogens. In an attempt to expand our knowledge of the repertoire of K. pneumoniae virulence factors, we also conducted an in vivo screen of the contribution of MarR-like transcriptional regulators to virulence in Chapter 3. We identified two previously unidentified regulators of virulence in K. pneumoniae, and have named these KvrA and KvrB. KvrA and KvrB are highly conserved across K. pneumoniae species. Both regulators regulated capsule expression and production, and this regulation appeared to be conserved in an isolate of a different capsule type. Interestingly, while KvrA and KvrB regulate capsule in a similar fashion, the in vivo kinetics of infection of the kvrA and kvrB mutants were quite distinct suggesting that the regulons of KvrA and KvrB are unique from each other. Because our studies focused on highly conserved virulence factors, our work has implications for the development of novel anti-Klebsiella therapeutics. Summer 2017 2017 Microbiology Biology Molecular biology bacteria, infection, pathogenesis, regulation, siderophores, virulence eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Virginia Miller Thesis advisor Thomas Kawula Thesis advisor Rob Maile Thesis advisor Bruce Cairns Thesis advisor Peggy Cotter Thesis advisor Janella Arthur Thesis advisor text Michelle Palacios Creator Department of Microbiology and Immunology School of Medicine Identification of conserved Klebsiella pneumoniae virulence factors Klebsiella pneumoniae is an urgent threat to public health due to nosocomial outbreaks of multi-drug resistant strains and the emergence of hypervirulent community acquired infections. Only in recent years have we gained a better understanding of the population structure of emergent clones and insight on the high level of strain-to-strain genomic variation K. pneumoniae strains display. While capsule and siderophores are considered primary virulence factors of K. pneumoniae, the number of siderophore types encoded and the capsule type can vary significantly from strain-to-strain. Thus, identifying highly conserved virulence mechanisms is essential for therapeutic development. This work focused on the use of a murine pneumonia model of infection and a sputum-derived isolate of K. pneumoniae to identify previously uncharacterized virulence factors. In Chapter 2, we describe how a serendipitous mutation led us to identify the periplasmic importer of enterobactin, FepB, as being a unique contributor to virulence. Interestingly, the contribution of FepB to virulence was greater than the contribution of enterobactin to virulence suggesting a greater role than enterobactin transport. Given that FepB is present in other pathogenic Enterobacteriaceae, our findings may be applicable to other pathogens. In an attempt to expand our knowledge of the repertoire of K. pneumoniae virulence factors, we also conducted an in vivo screen of the contribution of MarR-like transcriptional regulators to virulence in Chapter 3. We identified two previously unidentified regulators of virulence in K. pneumoniae, and have named these KvrA and KvrB. KvrA and KvrB are highly conserved across K. pneumoniae species. Both regulators regulated capsule expression and production, and this regulation appeared to be conserved in an isolate of a different capsule type. Interestingly, while KvrA and KvrB regulate capsule in a similar fashion, the in vivo kinetics of infection of the kvrA and kvrB mutants were quite distinct suggesting that the regulons of KvrA and KvrB are unique from each other. Because our studies focused on highly conserved virulence factors, our work has implications for the development of novel anti-Klebsiella therapeutics. 2017-08 2017 Microbiology Biology Molecular biology bacteria, infection, pathogenesis, regulation, siderophores, virulence eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Virginia Miller Thesis advisor Thomas Kawula Thesis advisor Rob Maile Thesis advisor Bruce Cairns Thesis advisor Peggy Cotter Thesis advisor Janella Arthur Thesis advisor text Michelle Palacios Creator Department of Microbiology and Immunology School of Medicine Identification of conserved Klebsiella pneumoniae virulence factors Klebsiella pneumoniae is an urgent threat to public health due to nosocomial outbreaks of multi-drug resistant strains and the emergence of hypervirulent community acquired infections. Only in recent years have we gained a better understanding of the population structure of emergent clones and insight on the high level of strain-to-strain genomic variation K. pneumoniae strains display. While capsule and siderophores are considered primary virulence factors of K. pneumoniae, the number of siderophore types encoded and the capsule type can vary significantly from strain-to-strain. Thus, identifying highly conserved virulence mechanisms is essential for therapeutic development. This work focused on the use of a murine pneumonia model of infection and a sputum-derived isolate of K. pneumoniae to identify previously uncharacterized virulence factors. In Chapter 2, we describe how a serendipitous mutation led us to identify the periplasmic importer of enterobactin, FepB, as being a unique contributor to virulence. Interestingly, the contribution of FepB to virulence was greater than the contribution of enterobactin to virulence suggesting a greater role than enterobactin transport. Given that FepB is present in other pathogenic Enterobacteriaceae, our findings may be applicable to other pathogens. In an attempt to expand our knowledge of the repertoire of K. pneumoniae virulence factors, we also conducted an in vivo screen of the contribution of MarR-like transcriptional regulators to virulence in Chapter 3. We identified two previously unidentified regulators of virulence in K. pneumoniae, and have named these KvrA and KvrB. KvrA and KvrB are highly conserved across K. pneumoniae species. Both regulators regulated capsule expression and production, and this regulation appeared to be conserved in an isolate of a different capsule type. Interestingly, while KvrA and KvrB regulate capsule in a similar fashion, the in vivo kinetics of infection of the kvrA and kvrB mutants were quite distinct suggesting that the regulons of KvrA and KvrB are unique from each other. Because our studies focused on highly conserved virulence factors, our work has implications for the development of novel anti-Klebsiella therapeutics. 2017 Microbiology Biology Molecular biology bacteria, infection, pathogenesis, regulation, siderophores, virulence eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Virginia Miller Thesis advisor Thomas Kawula Thesis advisor Rob Maile Thesis advisor Bruce Cairns Thesis advisor Peggy Cotter Thesis advisor Janella Arthur Thesis advisor text 2017-08 Michelle Palacios Creator Department of Microbiology and Immunology School of Medicine Identification of conserved Klebsiella pneumoniae virulence factors Klebsiella pneumoniae is an urgent threat to public health due to nosocomial outbreaks of multi-drug resistant strains and the emergence of hypervirulent community acquired infections. Only in recent years have we gained a better understanding of the population structure of emergent clones and insight on the high level of strain-to-strain genomic variation K. pneumoniae strains display. While capsule and siderophores are considered primary virulence factors of K. pneumoniae, the number of siderophore types encoded and the capsule type can vary significantly from strain-to-strain. Thus, identifying highly conserved virulence mechanisms is essential for therapeutic development. This work focused on the use of a murine pneumonia model of infection and a sputum-derived isolate of K. pneumoniae to identify previously uncharacterized virulence factors. In Chapter 2, we describe how a serendipitous mutation led us to identify the periplasmic importer of enterobactin, FepB, as being a unique contributor to virulence. Interestingly, the contribution of FepB to virulence was greater than the contribution of enterobactin to virulence suggesting a greater role than enterobactin transport. Given that FepB is present in other pathogenic Enterobacteriaceae, our findings may be applicable to other pathogens. In an attempt to expand our knowledge of the repertoire of K. pneumoniae virulence factors, we also conducted an in vivo screen of the contribution of MarR-like transcriptional regulators to virulence in Chapter 3. We identified two previously unidentified regulators of virulence in K. pneumoniae, and have named these KvrA and KvrB. KvrA and KvrB are highly conserved across K. pneumoniae species. Both regulators regulated capsule expression and production, and this regulation appeared to be conserved in an isolate of a different capsule type. Interestingly, while KvrA and KvrB regulate capsule in a similar fashion, the in vivo kinetics of infection of the kvrA and kvrB mutants were quite distinct suggesting that the regulons of KvrA and KvrB are unique from each other. Because our studies focused on highly conserved virulence factors, our work has implications for the development of novel anti-Klebsiella therapeutics. 2017 Microbiology Biology Molecular biology bacteria, infection, pathogenesis, regulation, siderophores, virulence eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Virginia Miller Thesis advisor Thomas Kawula Thesis advisor Rob Maile Thesis advisor Bruce Cairns Thesis advisor Peggy Cotter Thesis advisor Janella Arthur Thesis advisor text 2017-08 Michelle Palacios Creator Department of Microbiology and Immunology School of Medicine Identification of conserved Klebsiella pneumoniae virulence factors Klebsiella pneumoniae is an urgent threat to public health due to nosocomial outbreaks of multi-drug resistant strains and the emergence of hypervirulent community acquired infections. Only in recent years have we gained a better understanding of the population structure of emergent clones and insight on the high level of strain-to-strain genomic variation K. pneumoniae strains display. While capsule and siderophores are considered primary virulence factors of K. pneumoniae, the number of siderophore types encoded and the capsule type can vary significantly from strain-to-strain. Thus, identifying highly conserved virulence mechanisms is essential for therapeutic development. This work focused on the use of a murine pneumonia model of infection and a sputum-derived isolate of K. pneumoniae to identify previously uncharacterized virulence factors. In Chapter 2, we describe how a serendipitous mutation led us to identify the periplasmic importer of enterobactin, FepB, as being a unique contributor to virulence. Interestingly, the contribution of FepB to virulence was greater than the contribution of enterobactin to virulence suggesting a greater role than enterobactin transport. Given that FepB is present in other pathogenic Enterobacteriaceae, our findings may be applicable to other pathogens. In an attempt to expand our knowledge of the repertoire of K. pneumoniae virulence factors, we also conducted an in vivo screen of the contribution of MarR-like transcriptional regulators to virulence in Chapter 3. We identified two previously unidentified regulators of virulence in K. pneumoniae, and have named these KvrA and KvrB. KvrA and KvrB are highly conserved across K. pneumoniae species. Both regulators regulated capsule expression and production, and this regulation appeared to be conserved in an isolate of a different capsule type. Interestingly, while KvrA and KvrB regulate capsule in a similar fashion, the in vivo kinetics of infection of the kvrA and kvrB mutants were quite distinct suggesting that the regulons of KvrA and KvrB are unique from each other. Because our studies focused on highly conserved virulence factors, our work has implications for the development of novel anti-Klebsiella therapeutics. 2017 Microbiology Biology Molecular biology bacteria, infection, pathogenesis, regulation, siderophores, virulence eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Virginia Miller Thesis advisor Thomas Kawula Thesis advisor Rob Maile Thesis advisor Bruce Cairns Thesis advisor Peggy Cotter Thesis advisor Janella Arthur Thesis advisor text 2017-08 Michelle Palacios Creator Department of Microbiology and Immunology School of Medicine Identification of conserved Klebsiella pneumoniae virulence factors Klebsiella pneumoniae is an urgent threat to public health due to nosocomial outbreaks of multi-drug resistant strains and the emergence of hypervirulent community acquired infections. Only in recent years have we gained a better understanding of the population structure of emergent clones and insight on the high level of strain-to-strain genomic variation K. pneumoniae strains display. While capsule and siderophores are considered primary virulence factors of K. pneumoniae, the number of siderophore types encoded and the capsule type can vary significantly from strain-to-strain. Thus, identifying highly conserved virulence mechanisms is essential for therapeutic development. This work focused on the use of a murine pneumonia model of infection and a sputum-derived isolate of K. pneumoniae to identify previously uncharacterized virulence factors. In Chapter 2, we describe how a serendipitous mutation led us to identify the periplasmic importer of enterobactin, FepB, as being a unique contributor to virulence. Interestingly, the contribution of FepB to virulence was greater than the contribution of enterobactin to virulence suggesting a greater role than enterobactin transport. Given that FepB is present in other pathogenic Enterobacteriaceae, our findings may be applicable to other pathogens. In an attempt to expand our knowledge of the repertoire of K. pneumoniae virulence factors, we also conducted an in vivo screen of the contribution of MarR-like transcriptional regulators to virulence in Chapter 3. We identified two previously unidentified regulators of virulence in K. pneumoniae, and have named these KvrA and KvrB. KvrA and KvrB are highly conserved across K. pneumoniae species. Both regulators regulated capsule expression and production, and this regulation appeared to be conserved in an isolate of a different capsule type. Interestingly, while KvrA and KvrB regulate capsule in a similar fashion, the in vivo kinetics of infection of the kvrA and kvrB mutants were quite distinct suggesting that the regulons of KvrA and KvrB are unique from each other. Because our studies focused on highly conserved virulence factors, our work has implications for the development of novel anti-Klebsiella therapeutics. 2017 Microbiology Biology Molecular biology bacteria, infection, pathogenesis, regulation, siderophores, virulence eng Doctor of Philosophy Dissertation Microbiology and Immunology Virginia Miller Thesis advisor Thomas Kawula Thesis advisor Robert Maile Thesis advisor Bruce Cairns Thesis advisor Peggy Cotter Thesis advisor Janelle Arthur Thesis advisor text 2017-08 University of North Carolina at Chapel Hill Degree granting institution Michelle Palacios Creator Department of Microbiology and Immunology School of Medicine Identification of conserved Klebsiella pneumoniae virulence factors Klebsiella pneumoniae is an urgent threat to public health due to nosocomial outbreaks of multi-drug resistant strains and the emergence of hypervirulent community acquired infections. Only in recent years have we gained a better understanding of the population structure of emergent clones and insight on the high level of strain-to-strain genomic variation K. pneumoniae strains display. While capsule and siderophores are considered primary virulence factors of K. pneumoniae, the number of siderophore types encoded and the capsule type can vary significantly from strain-to-strain. Thus, identifying highly conserved virulence mechanisms is essential for therapeutic development. This work focused on the use of a murine pneumonia model of infection and a sputum-derived isolate of K. pneumoniae to identify previously uncharacterized virulence factors. In Chapter 2, we describe how a serendipitous mutation led us to identify the periplasmic importer of enterobactin, FepB, as being a unique contributor to virulence. Interestingly, the contribution of FepB to virulence was greater than the contribution of enterobactin to virulence suggesting a greater role than enterobactin transport. Given that FepB is present in other pathogenic Enterobacteriaceae, our findings may be applicable to other pathogens. In an attempt to expand our knowledge of the repertoire of K. pneumoniae virulence factors, we also conducted an in vivo screen of the contribution of MarR-like transcriptional regulators to virulence in Chapter 3. We identified two previously unidentified regulators of virulence in K. pneumoniae, and have named these KvrA and KvrB. KvrA and KvrB are highly conserved across K. pneumoniae species. Both regulators regulated capsule expression and production, and this regulation appeared to be conserved in an isolate of a different capsule type. Interestingly, while KvrA and KvrB regulate capsule in a similar fashion, the in vivo kinetics of infection of the kvrA and kvrB mutants were quite distinct suggesting that the regulons of KvrA and KvrB are unique from each other. Because our studies focused on highly conserved virulence factors, our work has implications for the development of novel anti-Klebsiella therapeutics. 2017 Microbiology Biology Molecular biology bacteria, infection, pathogenesis, regulation, siderophores, virulence eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Virginia Miller Thesis advisor Thomas Kawula Thesis advisor Rob Maile Thesis advisor Bruce Cairns Thesis advisor Peggy Cotter Thesis advisor Janella Arthur Thesis advisor text 2017-08 Michelle Palacios Creator Department of Microbiology and Immunology School of Medicine Identification of conserved Klebsiella pneumoniae virulence factors Klebsiella pneumoniae is an urgent threat to public health due to nosocomial outbreaks of multi-drug resistant strains and the emergence of hypervirulent community acquired infections. Only in recent years have we gained a better understanding of the population structure of emergent clones and insight on the high level of strain-to-strain genomic variation K. pneumoniae strains display. While capsule and siderophores are considered primary virulence factors of K. pneumoniae, the number of siderophore types encoded and the capsule type can vary significantly from strain-to-strain. Thus, identifying highly conserved virulence mechanisms is essential for therapeutic development. This work focused on the use of a murine pneumonia model of infection and a sputum-derived isolate of K. pneumoniae to identify previously uncharacterized virulence factors. In Chapter 2, we describe how a serendipitous mutation led us to identify the periplasmic importer of enterobactin, FepB, as being a unique contributor to virulence. Interestingly, the contribution of FepB to virulence was greater than the contribution of enterobactin to virulence suggesting a greater role than enterobactin transport. Given that FepB is present in other pathogenic Enterobacteriaceae, our findings may be applicable to other pathogens. In an attempt to expand our knowledge of the repertoire of K. pneumoniae virulence factors, we also conducted an in vivo screen of the contribution of MarR-like transcriptional regulators to virulence in Chapter 3. We identified two previously unidentified regulators of virulence in K. pneumoniae, and have named these KvrA and KvrB. KvrA and KvrB are highly conserved across K. pneumoniae species. Both regulators regulated capsule expression and production, and this regulation appeared to be conserved in an isolate of a different capsule type. Interestingly, while KvrA and KvrB regulate capsule in a similar fashion, the in vivo kinetics of infection of the kvrA and kvrB mutants were quite distinct suggesting that the regulons of KvrA and KvrB are unique from each other. Because our studies focused on highly conserved virulence factors, our work has implications for the development of novel anti-Klebsiella therapeutics. 2017 Microbiology Biology Molecular biology bacteria; infection; pathogenesis; regulation; siderophores; virulence eng Doctor of Philosophy Dissertation Microbiology and Immunology Virginia Miller Thesis advisor Thomas Kawula Thesis advisor Robert Maile Thesis advisor Bruce Cairns Thesis advisor Peggy Cotter Thesis advisor Janelle Arthur Thesis advisor text 2017-08 University of North Carolina at Chapel Hill Degree granting institution Michelle Palacios Creator Department of Microbiology and Immunology School of Medicine Identification of conserved Klebsiella pneumoniae virulence factors Klebsiella pneumoniae is an urgent threat to public health due to nosocomial outbreaks of multi-drug resistant strains and the emergence of hypervirulent community acquired infections. Only in recent years have we gained a better understanding of the population structure of emergent clones and insight on the high level of strain-to-strain genomic variation K. pneumoniae strains display. While capsule and siderophores are considered primary virulence factors of K. pneumoniae, the number of siderophore types encoded and the capsule type can vary significantly from strain-to-strain. Thus, identifying highly conserved virulence mechanisms is essential for therapeutic development. This work focused on the use of a murine pneumonia model of infection and a sputum-derived isolate of K. pneumoniae to identify previously uncharacterized virulence factors. In Chapter 2, we describe how a serendipitous mutation led us to identify the periplasmic importer of enterobactin, FepB, as being a unique contributor to virulence. Interestingly, the contribution of FepB to virulence was greater than the contribution of enterobactin to virulence suggesting a greater role than enterobactin transport. Given that FepB is present in other pathogenic Enterobacteriaceae, our findings may be applicable to other pathogens. In an attempt to expand our knowledge of the repertoire of K. pneumoniae virulence factors, we also conducted an in vivo screen of the contribution of MarR-like transcriptional regulators to virulence in Chapter 3. We identified two previously unidentified regulators of virulence in K. pneumoniae, and have named these KvrA and KvrB. KvrA and KvrB are highly conserved across K. pneumoniae species. Both regulators regulated capsule expression and production, and this regulation appeared to be conserved in an isolate of a different capsule type. Interestingly, while KvrA and KvrB regulate capsule in a similar fashion, the in vivo kinetics of infection of the kvrA and kvrB mutants were quite distinct suggesting that the regulons of KvrA and KvrB are unique from each other. Because our studies focused on highly conserved virulence factors, our work has implications for the development of novel anti-Klebsiella therapeutics. 2017 Microbiology Biology Molecular biology bacteria, infection, pathogenesis, regulation, siderophores, virulence eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Virginia Miller Thesis advisor Thomas Kawula Thesis advisor Robert Maile Thesis advisor Bruce Cairns Thesis advisor Peggy Cotter Thesis advisor Janelle Arthur Thesis advisor text 2017-08 Michelle Palacios Creator Department of Microbiology and Immunology School of Medicine Klebsiella pneumoniae is an urgent threat to public health due to nosocomial outbreaks of multi-drug resistant strains and the emergence of hypervirulent community acquired infections. Only in recent years have we gained a better understanding of the population structure of emergent clones and insight on the high level of strain-to-strain genomic variation K. pneumoniae strains display. While capsule and siderophores are considered primary virulence factors of K. pneumoniae, the number of siderophore types encoded and the capsule type can vary significantly from strain-to-strain. Thus, identifying highly conserved virulence mechanisms is essential for therapeutic development. This work focused on the use of a murine pneumonia model of infection and a sputum-derived isolate of K. pneumoniae to identify previously uncharacterized virulence factors. In Chapter 2, we describe how a serendipitous mutation led us to identify the periplasmic importer of enterobactin, FepB, as being a unique contributor to virulence. Interestingly, the contribution of FepB to virulence was greater than the contribution of enterobactin to virulence suggesting a greater role than enterobactin transport. Given that FepB is present in other pathogenic Enterobacteriaceae, our findings may be applicable to other pathogens. In an attempt to expand our knowledge of the repertoire of K. pneumoniae virulence factors, we also conducted an in vivo screen of the contribution of MarR-like transcriptional regulators to virulence in Chapter 3. We identified two previously unidentified regulators of virulence in K. pneumoniae, and have named these KvrA and KvrB. KvrA and KvrB are highly conserved across K. pneumoniae species. Both regulators regulated capsule expression and production, and this regulation appeared to be conserved in an isolate of a different capsule type. Interestingly, while KvrA and KvrB regulate capsule in a similar fashion, the in vivo kinetics of infection of the kvrA and kvrB mutants were quite distinct suggesting that the regulons of KvrA and KvrB are unique from each other. Because our studies focused on highly conserved virulence factors, our work has implications for the development of novel anti-Klebsiella therapeutics. 2017 Microbiology Biology Molecular biology bacteria; infection; pathogenesis; regulation; siderophores; virulence eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Virginia Miller Thesis advisor Thomas Kawula Thesis advisor Robert Maile Thesis advisor Bruce Cairns Thesis advisor Peggy Cotter Thesis advisor Janelle Arthur Thesis advisor text 2017-08 Palacios_unc_0153D_17319.pdf uuid:960f3335-1e04-48bc-989e-356e97f2aab4 2017-07-24T01:08:06Z proquest 2019-08-15T00:00:00 application/pdf 45768802 yes