| Membrane disruption by antimicrobial fatty acids releases low-molecular-weight proteins from Staphylococcus aureus. | |
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MedLine Citation:
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PMID: 22843840 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The skin represents an important barrier for pathogens and is known to produce fatty acids that are toxic toward gram-positive bacteria. A screen of fatty acids as growth inhibitors of Staphylococcus aureus revealed structure-specific antibacterial activity. Fatty acids like oleate (18:1Δ9) were nontoxic, whereas palmitoleate (16:1Δ9) was a potent growth inhibitor. Cells treated with 16:1Δ9 exhibited rapid membrane depolarization, the disruption of all major branches of macromolecular synthesis, and the release of solutes and low-molecular-weight proteins into the medium. Other cytotoxic lipids, such as glycerol ethers, sphingosine, and acyl-amines blocked growth by the same mechanisms. Nontoxic 18:1Δ9 was used for phospholipid synthesis, whereas toxic 16:1Δ9 was not and required elongation to 18:1Δ11 prior to incorporation. However, blocking fatty acid metabolism using inhibitors to prevent acyl-acyl carrier protein formation or glycerol-phosphate acyltransferase activity did not increase the toxicity of 18:1Δ9, indicating that inefficient metabolism did not play a determinant role in fatty acid toxicity. Nontoxic 18:1Δ9 was as toxic as 16:1Δ9 in a strain lacking wall teichoic acids and led to growth arrest and enhanced release of intracellular contents. Thus, wall teichoic acids contribute to the structure-specific antimicrobial effects of unsaturated fatty acids. The ability of poorly metabolized 16:1 isomers to penetrate the cell wall defenses is a weakness that has been exploited by the innate immune system to combat S. aureus. |
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Authors:
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Joshua B Parsons; Jiangwei Yao; Matthew W Frank; Pamela Jackson; Charles O Rock |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-07-27 |
Journal Detail:
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Title: Journal of bacteriology Volume: 194 ISSN: 1098-5530 ISO Abbreviation: J. Bacteriol. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-09-11 Completed Date: 2012-11-23 Revised Date: 2013-04-01 |
Medline Journal Info:
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Nlm Unique ID: 2985120R Medline TA: J Bacteriol Country: United States |
Other Details:
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Languages: eng Pagination: 5294-304 Citation Subset: IM |
Affiliation:
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Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE36231 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anti-Bacterial Agents
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chemistry,
pharmacology* Bacterial Proteins / genetics, metabolism* Cell Membrane / drug effects* Cytoplasm Fatty Acids / chemistry, pharmacology* Gene Expression Regulation, Bacterial / drug effects Microbial Sensitivity Tests Permeability Staphylococcus aureus / cytology*, drug effects*, metabolism Structure-Activity Relationship |
| Grant Support | |
ID/Acronym/Agency:
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CA21765/CA/NCI NIH HHS; GM034496/GM/NIGMS NIH HHS; R01 GM034496/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-Bacterial Agents; 0/Bacterial Proteins; 0/Fatty Acids |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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