An outer membrane enzyme encoded by Salmonella typhimurium lpxR that removes the 3′-acyloxyacyl moiety of lipid A

C. Michael Reynolds, Anthony A. Ribeiro, Sara C. McGrath, Robert J. Cotter, Christian R.H. Raetz, M. Stephen Trent

Research output: Contribution to journalArticlepeer-review

Abstract

The Salmonella and related bacteria modify the structure of the lipid A portion of their lipopolysaccharide in response to environmental stimuli. Some lipid A modifications are required for virulence and resistance to cationic antimicrobial peptides. We now demonstrate that membranes of Salmonella typhimurium contain a novel hydrolase that removes the 3′-acyloxyacyl residue of lipid A in the presence of 5 mM Ca2+. We have identified the gene encoding the S. typhimurium lipid A 3′-O-deacylase, designated lpxR, by screening an ordered S. typhimurium genomic DNA library, harbored in Escherichia coli K-12, for expression of Ca2+-dependent 3′-O-deacylase activity in membranes. LpxR is synthesized with an N-terminal type I signal peptide and is localized to the outer membrane. Mass spectrometry was used to confirm the position of lipid A deacylation in vitro and the release of the intact 3′-acyloxyacyl group. Heterologous expression of lpxR in the E. coli K-12 W3110, which lacks lpxR, resulted in production of significant amounts of 3′-O-deacylated lipid A in growing cultures. Orthologues of LpxR are present in the genomes of E. coli 0157:H7, Yersinia enterocolitica, Helicobacter pylori, and Vibrio cholerae. The function of LpxR is unknown, but it could play a role in pathogenesis because it might modulate the cytokine response of an infected animal.

Original languageEnglish (US)
Pages (from-to)21974-21987
Number of pages14
JournalJournal of Biological Chemistry
Volume281
Issue number31
DOIs
StatePublished - Aug 4 2006

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'An outer membrane enzyme encoded by Salmonella typhimurium lpxR that removes the 3′-acyloxyacyl moiety of lipid A'. Together they form a unique fingerprint.

Cite this