This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tran, A. X.
Right arrow Articles by Trent, M. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tran, A. X.
Right arrow Articles by Trent, M. S.

 Previous Article  |  Next Article 

Journal of Bacteriology, June 2006, p. 4531-4541, Vol. 188, No. 12
0021-9193/06/$08.00+0     doi:10.1128/JB.00146-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The Lipid A 1-Phosphatase of Helicobacter pylori Is Required for Resistance to the Antimicrobial Peptide Polymyxin

An X. Tran,1 Judy D. Whittimore,1 Priscilla B. Wyrick,1 Sara C. McGrath,2 Robert J. Cotter,2 and M. Stephen Trent1*

Department of Microbiology, J. H. Quillen College of Medicine, Johnson City, Tennessee 37614,1 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 212052

Received 26 January 2006/ Accepted 24 March 2006

Modification of the phosphate groups of lipid A with amine-containing substituents, such as phosphoethanolamine, reduces the overall net negative charge of gram-negative bacterial lipopolysaccharide, thereby lowering its affinity to cationic antimicrobial peptides. Modification of the 1 position of Helicobacter pylori lipid A is a two-step process involving the removal of the 1-phosphate group by a lipid A phosphatase, LpxEHP (Hp0021), followed by the addition of a phosphoethanolamine residue catalyzed by EptAHP (Hp0022). To demonstrate the importance of modifying the 1 position of H. pylori lipid A, we generated LpxEHP-deficient mutants in various H. pylori strains by insertion of a chloramphenicol resistance cassette into lpxEHP and examined the significance of LpxE with respect to cationic antimicrobial peptide resistance. Using both mass spectrometry analysis and an in vitro assay system, we showed that the loss of LpxEHP activity in various H. pylori strains resulted in the loss of modification of the 1 position of H. pylori lipid A, thus confirming the function of LpxEHP. Due to its unique lipid A structure, H. pylori is highly resistant to the antimicrobial peptide polymyxin (MIC > 250 µg/ml). However, disruption of lpxEHP in H. pylori results in a dramatic decrease in polymyxin resistance (MIC, 10 µg/ml). In conclusion, we have characterized the first gram-negative LpxE-deficient mutant and have shown the importance of modifying the 1 position of H. pylori lipid A for resistance to polymyxin.

* Corresponding author. Mailing address: Box 70579, Johnson City, TN 37614. Phone: (423) 439-6293. Fax: (423) 439-8044. E-mail: trentms{at}mail.etsu.edu.

Journal of Bacteriology, June 2006, p. 4531-4541, Vol. 188, No. 12
0021-9193/06/$08.00+0     doi:10.1128/JB.00146-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Cekic, C., Casella, C. R., Eaves, C. A., Matsuzawa, A., Ichijo, H., Mitchell, T. C. (2009). Selective Activation of the p38 MAPK Pathway by Synthetic Monophosphoryl Lipid A. J. Biol. Chem. 284: 31982-31991 [Abstract] [Full Text]  
  • Hankins, J. V., Trent, M. S. (2009). Secondary Acylation of Vibrio cholerae Lipopolysaccharide Requires Phosphorylation of Kdo. J. Biol. Chem. 284: 25804-25812 [Abstract] [Full Text]  
  • Zhou, P., Chandan, V., Liu, X., Chan, K., Altman, E., Li, J. (2009). Microwave-assisted sample preparation for rapid and sensitive analysis of H. pylori lipid A applicable to a single colony. J. Lipid Res. 50: 1936-1944 [Abstract] [Full Text]  
  • Stead, C. M., Beasley, A., Cotter, R. J., Trent, M. S. (2008). Deciphering the Unusual Acylation Pattern of Helicobacter pylori Lipid A. J. Bacteriol. 190: 7012-7021 [Abstract] [Full Text]  
  • Lamarche, M. G., Kim, S.-H., Crepin, S., Mourez, M., Bertrand, N., Bishop, R. E., Dubreuil, J. D., Harel, J. (2008). Modulation of Hexa-Acyl Pyrophosphate Lipid A Population under Escherichia coli Phosphate (Pho) Regulon Activation. J. Bacteriol. 190: 5256-5264 [Abstract] [Full Text]  
  • Zavascki, A. P., Goldani, L. Z., Li, J., Nation, R. L. (2007). Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review. J Antimicrob Chemother 60: 1206-1215 [Abstract] [Full Text]  
  • Trent, M. S., Stead, C. M., Tran, A. X., Hankins, J. V. (2006). Invited review: Diversity of endotoxin and its impact on pathogenesis. Innate Immunity 12: 205-223 [Abstract]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»