title: Correlation of Klebsiella pneumoniae comparative genetic analyses with virulence profiles in a murine respiratory disease model.
abstract: Klebsiella pneumoniae is a bacterial pathogen of worldwide importance and a significant contributor to multiple disease presentations associated with both nosocomial and community acquired disease. ATCC 43816 is a well-studied K. pneumoniae strain which is capable of causing an acute respiratory disease in surrogate animal models. In this study, we performed sequencing of the ATCC 43816 genome to support future efforts characterizing genetic elements required for disease. Furthermore, we performed comparative genetic analyses to the previously sequenced genomes from NTUH-K2044 and MGH 78578 to gain an understanding of the conservation of known virulence determinants amongst the three strains. We found that ATCC 43816 and NTUH-K2044 both possess the known virulence determinant for yersiniabactin, as well as a Type 4 secretion system (T4SS), CRISPR system, and an acetonin catabolism locus, all absent from MGH 78578. While both NTUH-K2044 and MGH 78578 are clinical isolates, little is known about the disease potential of these strains in cell culture and animal models. Thus, we also performed functional analyses in the murine macrophage cell lines RAW264.7 and J774A.1 and found that MGH 78578 (K52 serotype) was internalized at higher levels than ATCC 43816 (K2) and NTUH-K2044 (K1), consistent with previous characterization of the antiphagocytic properties of K1 and K2 serotype capsules. We also examined the three K. pneumoniae strains in a novel BALB/c respiratory disease model and found that ATCC 43816 and NTUH-K2044 are highly virulent (LD50<100 CFU) while MGH 78578 is relatively avirulent.
authors.affiliation: Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Ramy A
authors.initials: RA
authors.lastname: Fodah
authors.affiliation: Dental School, University of Louisville, Louisville, Kentucky, United States of America; College of Dentistry, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Jacob B
authors.initials: JB
authors.lastname: Scott
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Hok-Hei
authors.initials: HH
authors.lastname: Tam
authors.affiliation: The Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, Division of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio, United States of America; Departments of Physics and Chemistry & Biochemistry and Center for RNA Biology, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Pearlly
authors.initials: P
authors.lastname: Yan
authors.affiliation: Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Tia L
authors.initials: TL
authors.lastname: Pfeffer
authors.affiliation: The Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, Division of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio, United States of America; Departments of Physics and Chemistry & Biochemistry and Center for RNA Biology, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Ralf
authors.initials: R
authors.lastname: Bundschuh
authors.affiliation: Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, United States of America; Center for Predictive Medicine, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Warawa
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D004269:DNA, Bacterial / Q000235:genetics; D004195:Disease Models, Animal; D016680:Genome, Bacterial / Q000235:genetics; D007710:Klebsiella Infections / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000235:genetics*; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012140:Respiratory Tract Diseases / Q000382:microbiology*; D017422:Sequence Analysis, DNA / Q000379:methods; D014774:Virulence / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D037521:Virulence Factors