Regulated expression of virulence genes appears to be crucial for pathogens that encounter multiple environments during their lifecycles. This may be particularly true for environmental pathogens such as Listeria monocytogenes which must adapt to life in the outside world as well as to life within host cells. For some environmental bacterial pathogens, such as Vibrio cholera and Legionella pneumophila (Hammer and Swanson 1999; Krukonis and DiRita 2003), specific signals have been identified that serve as triggers for virulence gene expression within the host. Regulation of bacterial gene expression in response to changes in temperature, the presence or absence of metal ions, amino acid availability, and iron are some examples of signals used to identify the host environment from other environments for different pathogens (Garcia et al. 1996; Hammer and Swanson 1999; Konkel and Tilly 2000; Krukonis and DiRita 2003) and to direct the production of virulence gene products. How does the soil-loving L. monocytogenes mediate its transition from the dirt or drain pipe to the host? What changes in gene expression allow this bacterium to transform from a sedate life in silage into a potentially lethal assailant in humans?

Transcriptional regulation of gene expression represents an important mechanism for bacterial adaptation to new environments. Of the 201 putative transcriptional regulators identified via bioinformatics analyses of the L. monocy-togenes genome sequence (Glaser et al. 2001), positive regulatory factor A (PrfA) stands out for its central and essential role in regulating the expression of virulence gene products. PrfA was first identified as a regulatory factor required for hly transcription (Leimeister-Wachter et al. 1990), and it has since been shown to regulate the expression of a growing number of bacterial gene products directly associated with virulence. The absolute requirement of PrfA for L. monocytogenes pathogenesis was demonstrated utilizing strains with deletions or loss-of-function mutations within the prfA gene: such strains failed to replicate in the cytosol of host cells or to spread to adjacent cells, and were severely attenuated for virulence in animal models of infection (Leimeister-Wachter et al. 1990; Mengaud et al. 1991; Freitag et al. 1993). As PrfA is a critical component for the regulated expression of virulence factors in L. monocyto-genes, it is not surprising that the expression and production of this regulator is controlled at multiple levels, including transcriptional, posttranscriptional, and post translational mechanisms of regulation. This chapter will provide a brief overview of what is currently known regarding how L. monocytogenes controls the expression and activity of its central virulence regulator PrfA and discuss how this regulation impacts the expression of bacterial virulence factors. In addition to PrfA-dependent control mechanisms, recently identified regulatory elements that contribute to virulence gene expression in L. monocytogenes will also be described.

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