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Science 11 April 1997:
Vol. 276. no. 5310, pp. 250 - 253
DOI: 10.1126/science.276.5310.250
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Reports

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

Lin Guo, * Kheng B. Lim, * John S. Gunn, Brian Bainbridge, Richard P. Darveau, Murray Hackett, Samuel I. Miller dagger

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.

L. Guo, J. S. Gunn, S. I. Miller, Departments of Medicine and Microbiology, University of Washington, Seattle, WA 98195, USA.
K. B. Lim and M. Hackett, Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
B. Bainbridge and R. P. Darveau, Inflammation Department, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121, USA.
*   These authors contributed equally to this report.

dagger    To whom correspondence should be addressed. E-mail: millersi{at}u.washington.edu

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   Abstract »    Full Text »    PDF »
Quantitative proteomic analysis indicates increased synthesis of a quinolone by Pseudomonas aeruginosa isolates from cystic fibrosis airways.
T. Guina, S. O. Purvine, E. C. Yi, J. Eng, D. R. Goodlett, R. Aebersold, and S. I. Miller (2003)
PNAS 100, 2771-2776
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Enteric Salmonella Infection Inhibits Paneth Cell Antimicrobial Peptide Expression.
N. H. Salzman, M. M. Chou, H. de Jong, L. Liu, E. M. Porter, and Y. Paterson (2003)
Infect. Immun. 71, 1109-1115
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Solution structure and dynamics of the outer membrane enzyme PagP by NMR.
P. M. Hwang, W.-Y. Choy, E. I. Lo, L. Chen, J. D. Forman-Kay, C. R. H. Raetz, G. G. Prive, R. E. Bishop, and L. E. Kay (2002)
PNAS 99, 13560-13565
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Mutational Analysis of the Escherichia coli PhoQ Sensor Kinase: Differences with the Salmonella enterica Serovar Typhimurium PhoQ Protein and in the Mechanism of Mg2+ and Ca2+ Sensing.
A. G. Regelmann, J. A. Lesley, C. Mott, L. Stokes, and C. D. Waldburger (2002)
J. Bacteriol. 184, 5468-5478
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Mycobacterium tuberculosis phoP mutant: lipoarabinomannan molecular structure.
P. Ludwiczak, M. Gilleron, Y. Bordat, C. Martin, B. Gicquel, and G. Puzo (2002)
Microbiology 148, 3029-3037
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mig-14 Is a Salmonella Gene That Plays a Role in Bacterial Resistance to Antimicrobial Peptides.
I. E. Brodsky, R. K. Ernst, S. I. Miller, and S. Falkow (2002)
J. Bacteriol. 184, 3203-3213
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Mycobacterium tuberculosis Genes Induced during Infection of Human Macrophages.
E. Dubnau, P. Fontan, R. Manganelli, S. Soares-Appel, and I. Smith (2002)
Infect. Immun. 70, 2787-2795
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Two msbB Genes Encoding Maximal Acylation of Lipid A Are Required for Invasive Shigella flexneri to Mediate Inflammatory Rupture and Destruction of the Intestinal Epithelium.
H. d'Hauteville, S. Khan, D. J. Maskell, A. Kussak, A. Weintraub, J. Mathison, R. J. Ulevitch, N. Wuscher, C. Parsot, and P. J. Sansonetti (2002)
J. Immunol. 168, 5240-5251