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

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Science  11 Apr 1997:
Vol. 276, Issue 5310, pp. 250-253
DOI: 10.1126/science.276.5310.250

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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–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.

  • * These authors contributed equally to this report.

  • To whom correspondence should be addressed. E-mail: millersi{at}

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