Transcriptional Regulation of the virR Operon of the Intracellular Pathogen Rhodococcus equi

ThevirR operon, located on the virulence plasmid of the intracellular pathogenRhodococcus equi , contains five genes, two of which (virR andorf8 ) encode transcriptional regulators. The first gene of the operon (virR ), encoding a LysR-type transcriptional regulator, is transcribed at a constitutive low level, whereas the four downstream genes are induced by low pH and high growth temperature. Differential regulation of thevirR operon genes could not be explained by differential mRNA stability, as there were no major differences in mRNA half-lives of the transcripts representing each of the five genes within thevirR operon. Transcription ofvirR is driven by the PvirR promoter, with a transcription start site 53 bp upstream of thevirR initiation codon. The four genes downstream ofvirR are transcribed from PvirR and from a second promoter, Porf5 , located 585 bp downstream of thevirR initiation codon. VirR binds to a site overlapping the initiation codon ofvirR , resulting in negative autoregulation of thevirR gene, explaining its low constitutive transcription level. The Porf5 promoter is induced by high temperature and low pH, thus explaining the observed differential gene expression of thevirR operon. VirR has a positive effect on Porf5 activity, whereas the response regulator encoded byorf8 is not involved in regulating transcription of thevirR operon. The PvirR promoter is strikingly similar to those recognized by the principal sigma factors ofStreptomyces andMycobacterium , whereas the Porf5 promoter does not share sequence similarity with PvirR . This suggests that Porf5 is recognized by an alternative sigma factor.