Depletion of glucose activates catabolite repression during pneumonic plague

Abstract

Bacterial pathogenesis depends on changes in metabolic and virulence gene expression in response to changes within a pathogen's environment. The plaguecausing pathogen, Yersinia pestis, requires expression of the gene encoding the Pla protease for progression of pneumonic plague. The catabolite repressor protein Crp, a global transcriptional regulator, may serve as the activator of pla in response to changes within the lungs as disease progresses. By using gene reporter fusions, the spatial and temporal activation of the crp and pla promoters was measured in a mouse model of pneumonic plague. In the lungs, crp was highly expressed in bacteria found within large aggregates resembling biofilms, while pla expression increased over time independent of the aggregated state. Increased expression of crp and pla correlated with a reduction in lung glucose levels. Deletion of the glucosespecific phosphotransferase system EIIBC (PtsG) of Y. pestis rescued glucose levels in the lungs, resulting in reduced expression of both crp and pla. We propose that activation of pla expression during pneumonic plague is driven by an increase of both Crp and cAMP levels following consumption of available glucose in the lungs by Y. pestis. Thus, Crp operates as a sensor linking the nutritional environment of the host to regulation of virulence gene expression.