title: Regulation of lipid A modifications by Salmonella typhimurium virulence genes phoP-phoQ.
abstract: Bacterial pathogenesis requires proteins that sense host microenvironments and respond by regulating virulence gene transcription. For Salmonellae, one such regulatory system is PhoP-PhoQ, which regulates genes required for intracellular survival and resistance to cationic peptides. Analysis by mass spectrometry revealed that Salmonella typhimurium PhoP-PhoQ regulated structural modifications of lipid A, the host signaling portion of lipopolysaccharide (LPS), by the addition of aminoarabinose and 2-hydroxymyristate. Structurally modified lipid A altered LPS-mediated expression of the adhesion molecule E-selectin by endothelial cells and tumor necrosis factor-alpha expression by adherent monocytes. Thus, altered responses to environmentally induced lipid A structural modifications may represent a mechanism for bacteria to gain advantage within host tissues.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: L
authors.initials: L
authors.lastname: Guo
authors.forename: K B
authors.initials: KB
authors.lastname: Lim
authors.forename: J S
authors.initials: JS
authors.lastname: Gunn
authors.forename: B
authors.initials: B
authors.lastname: Bainbridge
authors.forename: R P
authors.initials: RP
authors.lastname: Darveau
authors.forename: M
authors.initials: M
authors.lastname: Hackett
authors.forename: S I
authors.initials: SI
authors.lastname: Miller
mesh_terms: D000215:Acylation; D001089:Arabinose / Q000031:analogs & derivatives / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005227:Fatty Acids / Q000032:analysis; D005798:Genes, Bacterial; D006801:Humans; D008050:Lipid A / Q000737:chemistry* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism; D012486:Salmonella typhimurium / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D019040:E-Selectin; D005227:Fatty Acids; D008050:Lipid A; D008070:Lipopolysaccharides; C079792:PhoQ protein, Bacteria; D014409:Tumor Necrosis Factor-alpha; C016982:aminoarabinose; C061064:PhoP protein, Bacteria; D001089:Arabinose