The multifaceted RisA regulon of Bordetella pertussis.
The whooping cough agent Bordetella pertussis regulates the production of its virulence factors by the BvgA/S system. Phosphorylated BvgA activates the virulence-activated genes (vags) and represses the expression of the virulence-repressed genes (vrgs) via the activation of the bvgR gene. In modulating conditions, with MgSO4, the BvgA/S system is inactive, and the vrgs are expressed. Here, we show that the expression of almost all vrgs depends on RisA, another transcriptional regulator. We also show that some vags are surprisingly no longer modulated by MgSO4 in the risA(-) background. RisA also regulates the expression of other genes, including chemotaxis and flagellar operons, iron-regulated genes, and genes of unknown function, which may or may not be controlled by BvgA/S. We identified RisK as the likely cognate RisA kinase and found that it is important for expression of most, but not all RisA-regulated genes. This was confirmed using the phosphoablative RisAD(60)N and the phosphomimetic RisAD(60)E analogues. Thus the RisA regulon adds a new layer of complexity to B. pertussis virulence gene regulation.
Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.|Univ. Lille, Lille, France.|Centre National de la Recherche Scientifique (CNRS), UMR 8204, Lille, France.|Institut National de la Santé et de la Recherche Médicale (Inserm), U1019, Lille, France.
Loïc
L
Coutte
Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.|Univ. Lille, Lille, France.|Centre National de la Recherche Scientifique (CNRS), UMR 8204, Lille, France.|Institut National de la Santé et de la Recherche Médicale (Inserm), U1019, Lille, France.
Ludovic
L
Huot
Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.|Univ. Lille, Lille, France.|Centre National de la Recherche Scientifique (CNRS), UMR 8204, Lille, France.|Institut National de la Santé et de la Recherche Médicale (Inserm), U1019, Lille, France.
Rudy
R
Antoine
Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.|Univ. Lille, Lille, France.|Centre National de la Recherche Scientifique (CNRS), UMR 8204, Lille, France.|Institut National de la Santé et de la Recherche Médicale (Inserm), U1019, Lille, France.
Stephanie
S
Slupek
Divison of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, FDA, Silver Spring, MD, USA.
Tod J
TJ
Merkel
Divison of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, FDA, Silver Spring, MD, USA.
Qing
Q
Chen
Divison of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, FDA, Silver Spring, MD, USA.
Scott
S
Stibitz
Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.|Univ. Lille, Lille, France.|Centre National de la Recherche Scientifique (CNRS), UMR 8204, Lille, France.|Institut National de la Santé et de la Recherche Médicale (Inserm), U1019, Lille, France.
David
D
Hot
Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.|Univ. Lille, Lille, France.|Centre National de la Recherche Scientifique (CNRS), UMR 8204, Lille, France.|Institut National de la Santé et de la Recherche Médicale (Inserm), U1019, Lille, France.
Camille
C
Locht
D001426:Bacterial Proteins / Q000235:genetics* / Q000502:physiology*; D001886:Bordetella pertussis / Q000235:genetics* / Q000472:pathogenicity; D015964:Gene Expression Regulation, Bacterial; D018698:Glutamic Acid / Q000737:chemistry; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D009876:Operon; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000502:physiology*; D018085:Regulon; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D059467:Transcriptome; D014774:Virulence / Q000235:genetics*
D001426:Bacterial Proteins; D011956:Receptors, Cell Surface; C114918:RisA protein, Bordetella; D014157:Transcription Factors; D018698:Glutamic Acid