CARBON-SOURCE REGULATION OF VIRULENCE GENE-EXPRESSION IN LISTERIA-MONOCYTOGENES

All known virulence genes of Listeria monocytogenes are under positive regulation by the transcription factor PrfA. Previous work employing the L. monocytogenes strain NCTC7973 suggested that the disaccharide c ellobiose might serve as a specific 'signature molecule' which functio ns to prevent activation of the PrfA-controlled regulon in a soil envi ronment, We have examined three other L. monocytogenes strains, 10403S , L028 and EGD, all commonly regarded as wild-type isolates, and find that NCTC7973 is anomalous with respect to the effect of carbohydrates on the expression of PrfA-controlled gene expression, In the case of 10403S, L028 and EGD, several other readily metabolized mono- and disa ccharides are as effective as cellobiose in repressing expression of t he PrfA-controlled gene hly, indicating that the cellobiose effect is not specific, and suggesting that NCTC7973 may be a partially deregula ted variant. Moreover, concentrations of cellobiose and other sugars r equired for repression of hly expression (>1 mM) were found to signifi cantly enhance growth of L. monocytogenes cultures, suggesting that th e repression phenomenon probably results from a metabolic effect of su gar utilization rather than a signal-sensing response. Thus the previo usly reported cellobiose effect may reflect an aspect of a more global mechanism of catabolite repression in L. monocytogenes. Although cell obiose represses expression of hly and plcA at the level of transcript accumulation, quantitative Western blot analysis indicates that cello biose has no effect on PrfA levels, These results are consistent with a model in which PrfA activity is controlled by interaction with a hyp othetical cofactor, the synthesis or depletion of which is responsive to the presence of readily metabolized carbohydrates.