RovM, a novel LysR‐type regulator of the virulence activator gene rovA, controls cell invasion, virulence and motility of Yersinia pseudotuberculosis

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Abstract
Summary: 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.