BfvR, an AraC-Family Regulator, Controls Biofilm Formation and pH6 Antigen Production in Opposite Ways in Yersinia pestis Biovar Microtus

Abstract

Biofilm formation is critical for blocking flea foregut and hence for transmission of Y. pestis by flea biting. In this study, we identified the regulatory role of the AraC-family transcriptional regulator BfvR (YPO1737 in strain CO92) in biofilm formation and virulence of Yersinia pestis biovar Microtus. Crystal violet staining, Caenorhabditis elegans biofilm assay, colony morphology assay, intracellular c-di-GMP concentration determination, and BALB/c mice challenge were employed to reveal that BfvR enhanced Y. pestis biofilm formation while repressed its virulence in mice. Further molecular biological assays demonstrated that BfvR directly stimulated the expression of hmsHFRS, waaAE-coaD, and hmsCDE, which, in turn, affected the production of exopolysaccharide, LPS, and c-di-GMP, respectively. In addition, BfvR directly and indirectly repressed psaABC and psaEF transcription, respectively. We concluded that the modulation of biofilm- and virulence-related genes by BfvR led to increased biofilm formation and reduced virulence of Y. pestis biovar Microtus.