title: Delivery of cardiolipins to the Salmonella outer membrane is necessary for survival within host tissues and virulence.
abstract: The outer membrane (OM) of Gram-negative bacteria is an asymmetric lipid bilayer that serves as a barrier to the environment. During infection, Gram-negative bacteria remodel their OM to promote survival and replication within host tissues. Salmonella rely on the PhoPQ two-component regulators to coordinate OM remodeling in response to environmental cues. In a screen for mediators of PhoPQ-regulated OM remodeling in Salmonella Typhimurium, we identified PbgA, a periplasmic domain-containing transmembrane protein, which binds cardiolipin glycerophospholipids near the inner membrane and promotes their PhoPQ-regulated trafficking to the OM. Purified-PbgA oligomers are tetrameric, and the periplasmic domain contains a globular region that binds to the OM in a PhoPQ-dependent manner. Thus, PbgA forms a complex that may bridge the envelope for regulated cardiolipin delivery. PbgA globular region-deleted mutant bacteria are severely attenuated for pathogenesis, suggesting that increased cardiolipin trafficking to the OM is necessary for Salmonella to survive within host tissues that activate PhoPQ.
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Zachary D
authors: ZD
authors: Dalebroux
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Mauna B
authors: MB
authors: Edrozo
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Richard A
authors: RA
authors: Pfuetzner
authors: Department of Molecular and Cellular Biochemistry, Indiana University Bloomington, 212 S. Hawthrone Drive, Bloomington, IN 47401, USA.
authors: Susanne
authors: S
authors: Ressl
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Bridget R
authors: BR
authors: Kulasekara
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Marie-Pierre
authors: MP
authors: Blanc
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA. Electronic address: millersi@uw.edu.
authors: Samuel I
authors: SI
authors: Miller
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002308:Cardiolipins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization; D012486:Salmonella typhimurium / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D002308:Cardiolipins; D008565:Membrane Proteins