Jimmy Regeimbal

Upon entering host cells, L. monocytogenes up-regulates expression of multiple virulence factors that allow bacteria to replicate efficiently and spread to adjacent cells. Most of these genes are located on a 10 kb pathogenicity island and are under the control of a master transcriptional activator, PrfA. One remaining question is how bacteria sense the intracellular environment and initiate PrfA-mediated activation of virulence genes. Several lines of evidence indicate that unknown host factors, both proteins and small molecules, serve as signals to alert L. monocytogenes to its arrival inside a host cell. Interestingly, these signals appear to be sensed by bacteria at multiple levels.

Recent findings suggest that PrfA may also function as a sensor, as there may be a small-molecule regulator that activates PrfA at the protein level. In addition, the 5’ untranslated regions (UTR) of multiple PrfA-regulated virulence genes may have a binding site for a host cell factor that further controls gene expression. Thus, there appears to be several levels of control within the PrfA regulon that have yet to be identified, and are host-factor dependent. By using a biochemical approach, I am attempting to fractionate host cells and identify new factors, both proteins and small molecules, which serve as signals that allow L. monocytogenes to appropriately regulate the expression of its virulence determinants.