Regulation of Lipid A Modifications by Salmonella typhimurium Virulence Genes phoP-phoQ

• Published in: Science (American Association for the Advancement of Science) Vol. 276; no. 5310; pp. 250 - 253
• Main Authors: Guo, Lin, Lim, Kheng B., Gunn, John S., Bainbridge, Brian, Darveau, Richard P., Hackett, Murray, Miller, Samuel I.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 11-04-1997; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Acylation; Arabinose - analogs & derivatives; Arabinose - metabolism; Bacteria; Bacteria, Pathogenic; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Biological and medical sciences; E-Selectin - biosynthesis; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Endotoxins; Fatty acids; Fatty Acids - analysis; Fundamental and applied biological sciences. Psychology; Genes; Genes, Bacterial; Genetic aspects; Humans; Ion traps; Ions; Lipid A - chemistry; Lipid A - metabolism; Lipids; Lipopolysaccharides - chemistry; Lipopolysaccharides - pharmacology; Mass spectra; Mass spectroscopy; Medical research; Microbiology; Monocytes - metabolism; Pathogenic bacteria; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Peptides; Phosphates; Salmonella; Salmonella typhimurium; Salmonella typhimurium - chemistry; Salmonella typhimurium - genetics; Salmonella typhimurium - metabolism; Salmonella typhimurium - pathogenicity; Scientific Concepts; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tumor Necrosis Factor-alpha - biosynthesis; Virulence; Virulence (Microbiology); Virulence - genetics; Pathogenicity; Chemical modification; Virulence; Lipopolysaccharide; Bacteria; Host agent relation; Structure function relationship; Salmonella typhimurium; Enterobacteriaceae
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.276.5310.250

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-hydroxy-myristate. Structurally modified lipid A altered LPS-mediated expression of the adhesion molecule E-selectin by endothelial cells and tumor necrosis factor-α 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.