Bordetella PlrSR regulatory system controls BvgAS activity and virulence in the lower respiratory tract

摘要: Bacterial pathogens coordinate virulence using two-component regulatory systems (TCS). The Bordetella gene (BvgAS) phosphorelay-type TCS controls expression of all known protein factor-encoding genes and is considered the "master regulator" in pertussis, causal agent related organisms, including broad host range pathogen bronchiseptica We recently discovered an additional sensor kinase, PlrS [for persistence lower respiratory tract (LRT) sensor], which required for B. LRT. Here, we show that BvgAS to become remain fully active mouse lungs but not nasal cavity, demonstrating coordinates specifically LRT even when rendered constitutively active, suggesting presence BvgAS-independent, PlrS-dependent factors are critical bacterial survival also human pertussis murine provide evidence most likely functions via putative cognate response regulator PlrR. These data support a model senses conditions present activates PlrR, maintenance activity essential BvgAS-independent functions. In addition providing major advance our understanding regulation Bordetella, has served as paradigm several decades, these results indicate existence previously unknown may serve new vaccine components therapeutic or diagnostic targets.