RovM, a novel LysR-type regulator of the virulence activator gene rovA, controls cell invasion, virulence and motility of Yersinia pseudotuberculosis.
RovA is a MarR-type transcriptional regulator that controls transcription of rovA, the expression of the primary invasive factor invasin and other virulence genes of Yersinia pseudotuberculosis in response to environmental signals. Using a genetic approach to identify regulatory components that negatively influence rovA expression, we identified a new LysR-type regulatory protein, designated RovM, which exhibits homology to the virulence regulator PecT/HexA of plant pathogenic Erwinia species. DNA-binding studies revealed that RovM interacts specifically with a short binding site between promoters P1 and P2 within the rovA regulatory region and negatively modulates rovA transcription in cooperation with the histone-like protein H-NS. The rovM gene itself is under positive autoregulatory control and is significantly induced during growth in minimal media as shown in regulation studies. Disruption of the rovM gene leads to a significant increase of RovA and invasin synthesis and enhances internalization of Y. pseudotuberculosis into host cells. Finally, we show that a Y. pseudotuberculosis rovM mutant is more virulent than wild type and higher numbers of the bacteria are detectable in gut-associated lymphatic tissues and organs in the mouse infection model system. In contrast, elevated levels of the RovM protein, which exert a positive effect on flagellar motility, severely attenuate the ability of Y. pseudotuberculosis to disseminate to deeper tissues. Together, our data show, that RovM is a key regulator implicated in the environmental control of virulence factors, which are crucial for the initiation of a Yersinia infection.
Heroven
Ann Kathrin
AK
Institut für Mikrobiologie, Technische Universität Braunschweig, 38106 Braunschweig, Germany.
Dersch
Petra
P
D018829:Adhesins, Bacterial / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial; D005809:Genes, Regulator; D051379:Mice; D008807:Mice, Inbred BALB C; D015534:Trans-Activators / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014774:Virulence / Q000235:genetics*; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; C405626:RovA protein, Yersinia; C517503:RovM protein, Yersinia pseudotuberculosis; D015534:Trans-Activators; D014157:Transcription Factors; C053476:invasin, Yersinia; C073470:LysR protein, Bacteria