The bvr Locus of Listeria monocytogenes Mediates Virulence Gene Repression by β-Glucosides

Abstract

ABSTRACTThe β-glucoside cellobiose has been reported to specifically repress the PrfA-dependent virulence geneshlyandplcAinListeria monocytogenesNCTC 7973. This led to the hypothesis that β-glucosides, sugars of plant origin, may act as signal molecules, preventing the expression of virulence genes ifL. monocytogenesis living in its natural habitat (soil). In three other laboratory strains (EGD, L028, and 10403S), however, the effect of cellobiose was not unique, and all fermentable carbohydrates repressedhly. This suggested that the downregulation of virulence genes by β-glucosides is not a specific phenomenon but, rather, an aspect of a global regulatory mechanism of catabolite repression (CR). We assessed the effect of carbohydrates on virulence gene expression in a panel of wild-type isolates ofL. monocytogenesby using the PrfA-dependent phospholipase C geneplcBas a reporter. Utilization of any fermentable sugar causedplcBrepression in wild-typeL. monocytogenes. However, an EGD variant was identified in which, as in NCTC 7973,plcBwas only repressed by β-glucosides. Thus, the regulation ofL. monocytogenesvirulence genes by sugars appears to be mediated by two separate mechanisms, one presumably involving a CR pathway and another specifically responding to β-glucosides. We have identified inL. monocytogenesa 4-kb operon,bvrABC, encoding an antiterminator of the BglG family (bvrA), a β-glucoside-specific enzyme II permease component of the phosphoenolpyruvate-sugar phosphotransferase system (bvrB), and a putative ADP-ribosylglycohydrolase (bvrC). Low-stringency Southern blots showed that this locus is absent from otherListeriaspp. Transcription ofbvrBwas induced by cellobiose and salicin but not by arbutin. Disruption of thebvroperon by replacing part ofbvrABwith an interposon abolished the repression by cellobiose and salicin but not that by arbutin. Our data indicate that thebvrlocus encodes a β-glucoside-specific sensor that mediates virulence gene repression upon detection of cellobiose and salicin. Bvr is the first sensory system found inL. monocytogenesthat is involved in environmental regulation of virulence genes.