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Deacylation and palmitoylation of lipid A by Salmonellae outer membrane enzymes modulate host signaling through Toll-like receptor 4

Department of Microbiology, University of Washington, Seattle, Washington, USA

Robert K. Ernst

Department of Medicine, University of Washington, Seattle, Washington, USA

Samuel I. Miller

Department of Microbiology, University of Washington, Seattle, Washington, USA, Department of Genome Sciences, University of Washington, Seattle, Washington, USA, millersi{at}u.washington.edu

The Salmonella typhimurium virulence gene products, PhoP/PhoQ sense host micro-environments to regulate the expression of a lipid A 3-O-deacylase, PagL, and a lipid A palmitoyltransferase, PagP. Therefore, deacylation and/or palmitoylation of lipid A could occur in Salmonellae adapted to host environments. The acylation state of lipid A can alter host recognition and signaling by Toll-like receptor (TLR) 4, and may play an important role in host defenses against Salmonellae infection. Deacylated lipid A, deacylated and palmitoylated lipid A, palmitoylated lipid A, and unmodified lipid A species were purified, and the activity was examined using cell lines expressing recombinant human or mouse TLR4. Compared with unmodified lipid A, the modified lipid A species are 10—100-fold less active. These results suggest that PagL and PagP modify lipid A to reduce TLR4-signaling as part of Salmonellae adaptation to the host environment.

Key Words: Deacylation • palmitoylation • lipid A • Salmonellae • outer membrane enzymes • Toll-like receptor 4

Journal of Endotoxin Research, Vol. 10, No. 6, 439-444 (2004)
DOI: 10.1177/09680519040100061001


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