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Journal of Bacteriology, June 2009, p. 3861-3868, Vol. 191, No. 12
0021-9193/09/$08.00+0     doi:10.1128/JB.01313-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Endotoxin, Capsule, and Bacterial Attachment Contribute to Neisseria meningitidis Resistance to the Human Antimicrobial Peptide LL-37{triangledown} ,{dagger}

Allison Jones,2,3* Miriam Geörg,1,2 Lisa Maudsdotter,1,2 and Ann-Beth Jonsson1,2

Department of Genetics, Microbiology and Toxicology, Stockholm University, SE-106 91 Stockholm, Sweden,1 Department of Medical Biochemistry and Microbiology, Box 582, Uppsala University, SE-751 23 Uppsala, Sweden,2 Biochemistry, Office of Laboratory and Scientific Services, Therapeutic Goods Administration, Australia3

Received 17 September 2008/ Accepted 3 April 2009

Pathogenic bacteria have evolved numerous mechanisms to evade the human immune system and have developed widespread resistance to traditional antibiotics. We studied the human pathogen Neisseria meningitidis and present evidence of novel mechanisms of resistance to the human antimicrobial peptide LL-37. We found that bacteria attached to host epithelial cells are resistant to 10 µM LL-37 whereas bacteria in solution or attached to plastic are killed, indicating that the cell microenvironment protects bacteria. The bacterial endotoxin lipooligosaccharide and the polysaccharide capsule contribute to LL-37 resistance, probably by preventing LL-37 from reaching the bacterial membrane, as more LL-37 reaches the bacterial membrane on both lipooligosaccharide-deficient and capsule-deficient mutants whereas both mutants are also more susceptible to LL-37 killing than the wild-type strain. N. meningitidis bacteria respond to sublethal doses of LL-37 and upregulate two of their capsule genes, siaC and siaD, which further results in upregulation of capsule biosynthesis.


* Corresponding author. Present address: Biochemistry, Office of Laboratory and Scientific Services, Therapeutic Goods Administration, Australia. Phone: 612 6232 8582. Fax: 612 6232 8531. E-mail: allison.jones{at}tga.gov.au

{triangledown} Published ahead of print on 17 April 2009.

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


Journal of Bacteriology, June 2009, p. 3861-3868, Vol. 191, No. 12
0021-9193/09/$08.00+0     doi:10.1128/JB.01313-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.