| Human transferrin confers serum resistance against Bacillus anthracis. | |
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MedLine Citation:
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PMID: 20615872 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The innate immune system in humans consists of both cellular and humoral components that collaborate to eradicate invading bacteria from the body. Here, we discover that the gram-positive bacterium Bacillus anthracis, the causative agent of anthrax, does not grow in human serum. Fractionation of serum by gel filtration chromatography led to the identification of human transferrin as the inhibiting factor. Purified transferrin blocks growth of both the fully virulent encapsulated B. anthracis Ames and the non-encapsulated Sterne strain. Growth inhibition was also observed in serum of wild-type mice but not of hypotransferrinemic mice that only have approximately 1% circulating transferrin levels. We were able to definitely assign the bacteriostatic activity of transferrin to its iron-binding function: neither iron-saturated transferrin nor a recombinant transferrin mutant unable to bind iron could inhibit growth of B. anthracis. Additional iron could restore bacterial growth in human serum. The observation that other important gram-positive pathogens are not inhibited by transferrin suggests they have evolved effective mechanisms to circumvent serum iron deprivation. These findings provide a better understanding of human host defense mechanisms against anthrax and provide a mechanistic basis for the antimicrobial activity of human transferrin. |
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Authors:
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Suzan H M Rooijakkers; Suzanne L Rasmussen; Shauna M McGillivray; Thomas B Bartnikas; Anne B Mason; Arthur M Friedlander; Victor Nizet |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-07-08 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-30 Completed Date: 2010-10-05 Revised Date: 2011-09-13 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 27609-13 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, University of California, San Diego, La Jolla, California 92093, USA. s.h.m.rooijakkers@umcutrecht.nl |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Bacterial Agents / pharmacology* Bacillus anthracis / drug effects*, growth & development Female Humans Immunity, Innate Iron / metabolism Mice Serum / immunology*, microbiology* Transferrin / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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AI077780/AI/NIAID NIH HHS; DK084122-01/DK/NIDDK NIH HHS; DK21739/DK/NIDDK NIH HHS; GM068524/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-Bacterial Agents; 11096-37-0/Transferrin; 7439-89-6/Iron |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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