BordetellaPlrSR regulatory system controls BvgAS activity and virulence in the lower respiratory tract.
Bacterial pathogens coordinate virulence using two-component regulatory systems (TCS). TheBordetellavirulence gene (BvgAS) phosphorelay-type TCS controls expression of all known protein virulence factor-encoding genes and is considered the "master virulence regulator" inBordetella pertussis, the causal agent of pertussis, and related organisms, including the broad host range pathogenBordetella bronchisepticaWe recently discovered an additional sensor kinase, PlrS [for persistence in the lower respiratory tract (LRT) sensor], which is required forB. bronchisepticapersistence in the LRT. Here, we show that PlrS is required for BvgAS to become and remain fully active in mouse lungs but not the nasal cavity, demonstrating that PlrS coordinates virulence specifically in the LRT. PlrS is required for LRT persistence even when BvgAS is rendered constitutively active, suggesting the presence of BvgAS-independent, PlrS-dependent virulence factors that are critical for bacterial survival in the LRT. We show that PlrS is also required for persistence of the human pathogenB. pertussisin the murine LRT and we provide evidence that PlrS most likely functions via the putative cognate response regulator PlrR. These data support a model in which PlrS senses conditions present in the LRT and activates PlrR, which controls expression of genes required for the maintenance of BvgAS activity and for essential BvgAS-independent functions. In addition to providing a major advance in our understanding of virulence regulation inBordetella, which has served as a paradigm for several decades, these results indicate the existence of previously unknown virulence factors that may serve as new vaccine components and therapeutic or diagnostic targets.
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
M Ashley
MA
Bone
Department of Biology, Westmont College, Santa Barbara, CA 93108.
Aaron J
AJ
Wilk
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Andrew I
AI
Perault
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Sara A
SA
Marlatt
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Erich V
EV
Scheller
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Rebecca
R
Anthouard
Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892.
Qing
Q
Chen
Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892.
Scott
S
Stibitz
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; peggy_cotter@med.unc.edu sjulio@westmont.edu.
Peggy A
PA
Cotter
Department of Biology, Westmont College, Santa Barbara, CA 93108; peggy_cotter@med.unc.edu sjulio@westmont.edu.
Steven M
SM
Julio
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D016950:Bordetella bronchiseptica / Q000235:genetics*; D001886:Bordetella pertussis / Q000235:genetics / Q000472:pathogenicity*; D002460:Cell Line; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D012137:Respiratory System / Q000382:microbiology*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism
D001426:Bacterial Proteins; D037521:Virulence Factors
Bordetella; gene regulation; respiratory infection; two-component system; virulence