Endotoxin, capsule, and bacterial attachment contribute to Neisseria meningitidis resistance to the human antimicrobial peptide LL-37.
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 microM 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.
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. allison.jones@tga.gov.au
Allison
A
Jones
Miriam
M
Geörg
Lisa
L
Maudsdotter
Ann-Beth
AB
Jonsson
D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001422:Bacterial Adhesion; D016667:Bacterial Capsules / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D054804:Cathelicidins; D024881:Drug Resistance, Bacterial; D004731:Endotoxins / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008585:Meningitis, Meningococcal / Q000382:microbiology; D050296:Microbial Viability / Q000187:drug effects; D009345:Neisseria meningitidis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D054804:Cathelicidins; D004731:Endotoxins