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Listeria monocytogenes is a gram-positive bacterium that lives within soil and decaying plant material but is also capable of transitioning into a deadly pathogen following ingestion by mammals. The bacterium makes the transition from outside environment to host via the coordinate regulation of virulence gene products that enable bacterial replication within host cells. PrfA is transcriptional activator that is required for the expression of nearly all identified L. monocytogenes virulence gene products. The expression of the prfA gene and the activity of the PrfA protein are carefully regulated by multiple mechanisms within L. monocytogenes. Two promoters function to provide the initial levels of PrfA that direct bacterial escape from host cell vacuoles, whereas a third promoter contributes to high level expression of prfA to promote spread of intracellular bacteria to adjacent host cells. The synthesis of PrfA protein is temperature-regulated such that prfA mRNA secondary structure prevents protein translation at low temperatures. An additional mechanism of control exists to regulate PrfA activity as PrfA appears to require the binding of a cofactor for full activation. Strains containing PrfA mutant proteins that are locked into a PrfA-activated state are fully virulent in animal models of infection, but are compromised for bacterial fitness outside of the host. It therefore appears that L. monocytogenes must maintain a balance between life in the host and life in the outside environment. Analyses of the L. monocytogenes genome sequence and microarray analysis indicate that additional gene products are subject to PrfA regulation either via direct interaction with PrfA or indirectly as the result of another PrfA-activated factor. [ABSTRACT FROM AUTHOR]