Cathelicidin administration protects mice from Bacillus anthracis spore challenge.
Cathelicidins are a family of cationic peptides expressed in mammals that possess numerous bactericidal and immunomodulatory properties. In vitro analyses showed that human, mouse, and pig cathelicidins inhibited Bacillus anthracis bacterial growth at micromolar concentrations in the presence or absence of capsule. Combined in vitro analyses of the effects of each peptide on spore germination and vegetative outgrowth by time lapse phase contrast microscopy, transmission electron microscopy, and flow cytometric analysis showed that only the pig cathelicidin was capable of directly arresting vegetative outgrowth and killing the developing bacilli within the confines of the exosporium. C57BL/6 mice were protected from spore-induced death by each cathelicidin in a time- and dose-dependent manner. Protection afforded by the porcine cathelicidin was due to its bactericidal effects, whereas the human and mouse cathelicidins appeared to mediate protection through increased recruitment of neutrophils to the site of infection. These findings suggest that cathelicidins might be utilized to augment the initial innate immune response to B. anthracis spore exposure and prevent the development of anthrax.
Lisanby
Mark W
MW
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Swiecki
Melissa K
MK
Dizon
Brian L P
BL
Pflughoeft
Kathryn J
KJ
Koehler
Theresa M
TM
Kearney
John F
JF
D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use* / Q000633:toxicity; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage* / Q000627:therapeutic use* / Q000633:toxicity; D001408:Bacillus anthracis / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D013171:Spores, Bacterial / Q000187:drug effects / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D013552:Swine; D014774:Virulence / Q000187:drug effects / Q000276:immunology; D054804:Cathelicidins
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins
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