Evidence for expressional crosstalk between the central virulence regulator PrfA and the stress response mediator ClpC in Listeria monocytogenes.

Abstract

Virulence is a multifactorial trait which depends on the coordinated expression of many bacterial products, hence it is to be expected that the regulatory circuits that control the relevant genetic determinants are somehow interconnected. Two pleiotropic regulatory elements acting at different levels, the transcription factor PrfA which controls virulence gene expression and the potential chaperone ClpC which is involved in tolerance to environmental stress, are required for Listeria monocytogenes survival within the host. We analyzed the influence of PrfA on clpC expression in L. monocytogenes. clpC transcription is maximal under heat-shock conditions, i.e. at 42 degrees C, and is very weak or undetectable at 37 degrees C. In a prfA* mutant which constitutively overexpresses PrfA and PrfA-dependent virulence genes, clpC transcription dropped to basal levels during exponential growth at 42 degrees C. This repression was not observed during stationary phase, indicating growth phase-dependent regulation of clpC. Culture in charcoal-treated medium, which triggers in wild-type strains the transcriptional activation of the PrfA regulon, also caused a strong downregulation of clpC. Moreover, in a prfA deletion mutant, clpC transcription during exponential growth at 37 degrees C was clearly enhanced, reaching the same high levels of the wild-type at 42 degrees C. Overall, our results indicate that clpC expression is negatively controlled at the transcriptional level, directly or indirectly, by the central virulence regulator PrfA.