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

Microb Pathog. 2011 Jun;50(6):314-21. doi: 10.1016/j.micpath.2011.02.005. Epub 2011 Feb 12.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Gastrointestinal Diseases / microbiology
  • Gene Deletion
  • Gene Expression Regulation, Bacterial
  • Genetic Variation
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Operon*
  • Plague / microbiology
  • Virulence / genetics
  • Yersinia pestis / genetics*
  • Yersinia pestis / pathogenicity*
  • Yersinia pseudotuberculosis / genetics*
  • Yersinia pseudotuberculosis / pathogenicity*
  • Yersinia pseudotuberculosis Infections / microbiology

Substances

  • Bacterial Proteins
  • PhoQ protein, Bacteria
  • PhoP protein, Bacteria