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The importance of the Rcs phosphorelay in the survival and pathogenesis of the enteropathogenic yersiniae

David J. Clarke^2,

¹ Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
² Department of Biology and Biochemistry, University of Bath, BA2 7AY, UK

Correspondence
Brendan W. Wren
Brendan.Wren{at}lshtm.ac.uk

The human-pathogenic yersiniae represent an ideal species group to study the evolution of highly virulent bacteria, with Yersinia pestis having emerged from the enteropathogen Y. pseudotuberculosis an estimated 20 000 years ago. Sequence data reveal that the Y. pestis genome is in the early stages of decay and contains hundreds of non-functioning pseudogenes, some of which may be important in the enteric lifestyle of Y. pseudotuberculosis. Bioinformatic analysis of pseudogenes from seven Y. pestis genome sequences identified rcsD as a gene disrupted early in the evolution of this organism. This phosphotransfer protein is part the of the Rcs phosphorelay, a two-component system present in the Enterobacteriaceae which has been shown to regulate the expression of capsular polysaccharide and other virulence determinants in several species including Escherichia coli and Salmonella. Using microarray analysis, we determined that the Y. pseudotuberculosis Rcs phosphorelay regulates the expression of 136 coding sequences, of which 60 % are predicted to affect the cell envelope. Several putative virulence determinants were identified as being regulated by this phosphorelay, along with proteins involved in biofilm formation, motility, mammalian cell adhesion and stress survival. Phenotypic assays on defined mutants confirmed a role for the phosphorelay in these processes in both Y. pseudotuberculosis and Y. enterocolitica.

Present address: Department of Microbiology, University College Cork, Cork, Ireland.

The microarray data for this study have been submitted to BUGSBase and ArrayExpress with accession number E-BUGS-57.

The online version of this paper includes supplementary material on the verification of the microarray data by the use of Lux constructs of two members of the proposed Y. pseudotuberculosis Rcs regulon.