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Journal of Bacteriology, November 2008, p. 7012-7021, Vol. 190, No. 21
0021-9193/08/$08.00+0     doi:10.1128/JB.00667-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Deciphering the Unusual Acylation Pattern of Helicobacter pylori Lipid A{triangledown} ,{dagger}

Christopher M. Stead,1 Ashley Beasley,2 Robert J. Cotter,2 and M. Stephen Trent1,3*

Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia 30912,1 Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205,2 Department of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, Texas 787123

Received 13 May 2008/ Accepted 20 August 2008

The synthesis of "typical" hexa-acylated lipid A occurs via a nine-step enzymatic pathway, which is generally well conserved throughout all gram-negative bacteria. One exception to the rule is Helicobacter pylori, which has only eight homologs to the nine lipid A biosynthetic enzymes. The discrepancy occurs toward the end of the pathway, with H. pylori containing only a single putative secondary acyltransferase encoded by jhp0265. In Escherichia coli K-12, two late acyltransferases, termed LpxL and LpxM, are required for the biosynthesis of hexa-acylated lipid A. Detailed biochemical and genetic analyses reveal that H. pylori Jhp0265 (the protein encoded by jhp0265) is in fact an LpxL homolog, capable of transferring a stearoyl group to the hydroxyl group of the 2' linked fatty acyl chain of lipid A. Despite the lack of a homolog to LpxM in the H. pylori genome, the organism synthesizes a hexa-acylated lipid A species, suggesting that an equivalent enzyme exists. Using radiolabeled lipid A substrates and acyl-acyl carrier protein as the fatty acyl donor, we were able to confirm the presence of a second H. pylori late acyl transferase by biochemical assays. After synthesis of the hexa-acylated lipid A species, several modification enzymes then function to produce the major lipid A species of H. pylori that is tetra-acylated. Jhp0634 was identified as an outer membrane deacylase that removes the 3'-linked acyl chains of H. pylori lipid A. Together, this work elucidates the biochemical machinery required for the acylation and deacylation of the lipid A domain of H. pylori lipopolysaccharide.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, TX 78712. Phone: (512) 475-6128. Fax: (512) 471-7088. E-mail: strent{at}mail.utexas.edu

{triangledown} Published ahead of print on 29 August 2008.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.

Journal of Bacteriology, November 2008, p. 7012-7021, Vol. 190, No. 21
0021-9193/08/$08.00+0     doi:10.1128/JB.00667-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Rutten, L., Mannie, J.-P. B. A., Stead, C. M., Raetz, C. R. H., Reynolds, C. M., Bonvin, A. M. J. J., Tommassen, J. P., Egmond, M. R., Trent, M. S., Gros, P. (2009). Active-site architecture and catalytic mechanism of the lipid A deacylase LpxR of Salmonella typhimurium. Proc. Natl. Acad. Sci. USA 106: 1960-1964 [Abstract] [Full Text]  


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