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Journal of Bacteriology, February 2009, p. 1311-1319, Vol. 191, No. 4
0021-9193/09/$08.00+0     doi:10.1128/JB.01345-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Bacillus anthracis Protein MprF Is Required for Synthesis of Lysylphosphatidylglycerols and for Resistance to Cationic Antimicrobial Peptides {triangledown} ,{dagger}

Shalaka Samant,1,{ddagger} Fong-Fu Hsu,2 Alexander A. Neyfakh,1,§ and Hyunwoo Lee1*

Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, M/C 870, 900 S. Ashland Ave., Chicago, Illinois 60607,1 Mass Spectrometry Resource, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, Washington University School of Medicine, St. Louis, Missouri 631102

Received 26 September 2008/ Accepted 25 November 2008

During inhalational anthrax, Bacillus anthracis survives and replicates in alveolar macrophages, followed by rapid invasion into the host's bloodstream, where it multiplies to cause heavy bacteremia. B. anthracis must therefore defend itself from host immune functions encountered during both the intracellular and the extracellular stages of anthrax infection. In both of these niches, cationic antimicrobial peptides are an essential component of the host's innate immune response that targets B. anthracis. However, the genetic determinants of B. anthracis contributing to resistance to these peptides are largely unknown. Here we generated Tn917 transposon mutants in the {Delta}ANR strain (pXO1– pXO2–) of B. anthracis and screened them for altered protamine susceptibility. A protamine-sensitive mutant identified carried the transposon inserted in the BA1486 gene encoding a putative membrane protein homologous to MprF known in several gram-positive pathogens. A mutant strain with the BAS1375 gene (the orthologue of BA1486) deleted in the Sterne 34F2 strain (pXO1+ pXO2–) of B. anthracis exhibited hypersusceptibility not only to protamine but also to {alpha}-helical cathelicidin LL-37 and β-sheet defensin human neutrophil peptide 1 compared to the wild-type Sterne strain. Analysis of membrane lipids using isotopic labeling demonstrated that the BAS1375 deletion mutant is unable to synthesize lysinylated phosphatidylglycerols, and this defect is rescued by genetic complementation. Further, we determined the structures of these lysylphosphatidylglycerols by using various mass spectrometric analyses. These results demonstrate that in B. anthracis a functional MprF is required for the biosynthesis of lysylphosphatidylglycerols, which is critical for resistance to cationic antimicrobial peptides.

* Corresponding author. Mailing address: Center for Pharmaceutical Biotechnology, University of Illinois at Chicago (m/c 870), 900 S. Ashland Ave., MBRB #3018, Chicago, IL 60607. Phone: (312) 996-3371. Fax: (312) 413-9303. E-mail: hlee31{at}uic.edu

{triangledown} Published ahead of print on 12 December 2008.

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

{ddagger} Present address: Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Ave., New Haven, CT 06511.

§ Deceased 20 April 2006.

Journal of Bacteriology, February 2009, p. 1311-1319, Vol. 191, No. 4
0021-9193/09/$08.00+0     doi:10.1128/JB.01345-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Roy, H., Ibba, M. (2009). Broad Range Amino Acid Specificity of RNA-dependent Lipid Remodeling by Multiple Peptide Resistance Factors. J. Biol. Chem. 284: 29677-29683 [Abstract] [Full Text]  


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