Document Detail

Membrane disruption by antimicrobial fatty acids releases low-molecular-weight proteins from Staphylococcus aureus.
MedLine Citation:
PMID:  22843840     Owner:  NLM     Status:  MEDLINE    
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.
Joshua B Parsons; Jiangwei Yao; Matthew W Frank; Pamela Jackson; Charles O Rock
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-27
Journal Detail:
Title:  Journal of bacteriology     Volume:  194     ISSN:  1098-5530     ISO Abbreviation:  J. Bacteriol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-11     Completed Date:  2012-11-23     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  2985120R     Medline TA:  J Bacteriol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5294-304     Citation Subset:  IM    
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
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MeSH Terms
Anti-Bacterial Agents / chemistry,  pharmacology*
Bacterial Proteins / genetics,  metabolism*
Cell Membrane / drug effects*
Fatty Acids / chemistry,  pharmacology*
Gene Expression Regulation, Bacterial / drug effects
Microbial Sensitivity Tests
Staphylococcus aureus / cytology*,  drug effects*,  metabolism
Structure-Activity Relationship
Grant Support
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Bacterial Proteins; 0/Fatty Acids

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