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

In this study, we revealed the regulatory role of the AraC-family transcriptional regulator BfvR (YPO1737) in biofilm formation and virulence of Yersinia pestis. Phenotypic assays showed that BfvR enhanced Y. pestis biofilm formation and 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, which affected virulence by possibly interfering with bacterial entry into pulmonary epithelial cells. We speculated that the modulation of biofilm- and virulence-related genes by BfvR leads to biofilm formation and the reduced virulence of Y. pestis. Biofilm formation is critical for blocking flea foregut and hence for transmission of Y. pestis by flea biting. The AraC-family transcriptional regulator BfvR is found to regulate biofilm-associated genes is important for understanding the biofilm formation of Y. pestis in flea foregut. This paper also revealed that BfvR reduced Y. pestis virulence through regulating virulence-associated genes. These findings demonstrated the balanced role of the regulator BfvR in biofilm formation and virulence of Y. pestis.