title: The role of the phoPQ operon in the pathogenesis of the fully virulent CO92 strain of Yersinia pestis and the IP32953 strain of Yersinia pseudotuberculosis.
abstract: At the genomic level, Yersinia pestis and Yersinia pseudotuberculosis are nearly identical but cause very different diseases. Y. pestis is the etiologic agent of plague; whereas Y. pseudotuberculosis causes a gastrointestinal infection primarily after the consumption of contaminated food. In many gram-negative pathogenic bacteria, PhoP is part of a two-component global regulatory system in which PhoQ serves as the sensor kinase, and PhoP is the response regulator. PhoP is known to activate a number of genes in many bacteria related to virulence. To determine the role of the PhoPQ proteins in Yersinia infections, primarily using aerosol challenge models, the phoP gene was deleted from the chromosome of the CO92 strain of Y. pestis and the IP32953 strain of Y. pseudotuberculosis, leading to a polar mutation of the phoPQ operon. We demonstrated that loss of phoPQ from both strains leads to a defect in intracellular growth and/or survival within macrophages. These in vitro data would suggest that the phoPQ mutants would be attenuated in vivo. However, the LD(50) for the Y. pestis mutant did not differ from the calculated LD(50) for the wild-type CO92 strain for either the bubonic or pneumonic murine models of infection. In contrast, mice challenged by aerosol with the Y. pseudotuberculosis mutant had a LD(50) value 40× higher than the wild-type strain. These results demonstrate that phoPQ are necessary for full virulence by aerosol infection with the IP32953 strain of Y. pseudotuberculosis. However, the PhoPQ proteins do not play a significant role in infection with a fully virulent strain of Y. pestis.
authors.affiliation: Bacteriology Division, The United States Army of Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702, United States. joel.a.bozue@us.army.mil
authors.forename: Joel
authors.initials: J
authors.lastname: Bozue
authors.forename: Sherry
authors.initials: S
authors.lastname: Mou
authors.forename: Krishna L
authors.initials: KL
authors.lastname: Moody
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Cote
authors.forename: Sylvia
authors.initials: S
authors.lastname: Trevino
authors.forename: David
authors.initials: D
authors.lastname: Fritz
authors.forename: Patricia
authors.initials: P
authors.lastname: Worsham
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000382:microbiology; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D014644:Genetic Variation; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009876:Operon; D010930:Plague / Q000382:microbiology; D014774:Virulence / Q000235:genetics; D015010:Yersinia pestis / Q000235:genetics* / Q000472:pathogenicity*; D015011:Yersinia pseudotuberculosis / Q000235:genetics* / Q000472:pathogenicity*; D015012:Yersinia pseudotuberculosis Infections / Q000382:microbiology
chemical_list: D001426:Bacterial Proteins; C079792:PhoQ protein, Bacteria; C061064:PhoP protein, Bacteria