Interference of Components of the Phosphoenolpyruvate Phosphotransferase System with the Central Virulence Gene Regulator PrfA ofListeria monocytogenes

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Abstract
Analysis ofListeria monocytogenes ptsH,hprK, andccpAmutants defective in carbon catabolite repression (CCR) control revealed significant alterations in the expression of PrfA-dependent genes. ThehprKmutant showed high up-regulation of PrfA-dependent virulence genes upon growth in glucose-containing medium whereas expression of these genes was even slightly down-regulated in theccpAmutant compared to the wild-type strain. TheptsHmutant could only grow in a rich culture medium, and here the PrfA-dependent genes were up-regulated as in thehprKmutant. As expected, HPr-Ser-P was not produced in thehprKandptsHmutants and synthesized at a similar level in theccpAmutant as in the wild-type strain. However, no direct correlation was found between the level of HPr-Ser-P or HPr-His-P and PrfA activity whenL. monocytogeneswas grown in minimal medium with different phosphotransferase system (PTS) carbohydrates. Comparison of the transcript profiles of thehprKandccpAmutants with that of the wild-type strain indicates that the up-regulation of the PrfA-dependent virulence genes in thehprKmutant correlates with the down-regulation of genes known to be controlled by the efficiency of PTS-mediated glucose transport. Furthermore, growth in the presence of the non-PTS substrate glycerol results in high PrfA activity. These data suggest that it is not the component(s) of the CCR or the common PTS pathway but, rather, the component(s) of subsequent steps that seem to be involved in the modulation of PrfA activity.