RovA, a global regulator of Yersinia pestis, specifically required for bubonic plague

Jason S. Cathelyn, Seth D. Crosby, Wyndham W. Lathem, William E. Goldman, Virginia L. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

The pathogenic species of Yersinia contain the transcriptional regulator RovA. In Yersinia pseudotuberculosis and Yersinia enterocolitica, RovA regulates expression of the invasion factor invasin (inv), which mediates translocation across the intestinal epithelium. A Y. enterocolitica rovA mutant has a significant decrease in virulence by LD50 analysis and an altered rate of dissemination compared with either wild type or an inv mutant, suggesting that RovA regulates multiple virulence factors. Here, we show the involvement of RovA in the virulence of Yersinia pestis, which naturally lacks a functional inv gene. A Y. pestis ΔrovA mutant is attenuated ≈80-fold by LD50 and is defective in dissemination/colonization of spleens and lungs after s.c. inoculation. However, the ΔrovA mutant is only slightly attenuated when given via an intranasal or i.p. route, indicating a more important role for RovA in bubonic plague than pneumonic plague or systemic infection. Microarray analysis was used to define the RovA regulon. The psa locus was among the most highly down-regulated loci in the ΔrovA mutant. A Δpsa/4 mutant had a significant dissemination defect after s.c. infection but only slight attenuation by the pneumonic-disease model, closely mimicking the virulence defect seen with the ΔrovA mutant. DNA-binding studies revealed that RovA specifically interacts with the psaE and psaA promoter regions, indicating a direct role for RovA in regulating this locus. Thus, RovA appears to be a global transcription factor in Y. pestis and, through its regulatory influence on genes such as psaEFABC, contributes to the virulence of Y. pestis.

Original languageEnglish (US)
Pages (from-to)13514-13519
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number36
DOIs
StatePublished - Sep 5 2006

Keywords

  • CUS-2 phage
  • IcmF-associated homologous protein
  • MarR/SlyA
  • pH 6 antigen

ASJC Scopus subject areas

  • General

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