Arachidonic Acid Kills Staphylococcus aureus through a Lipid Peroxidation Mechanism

Author:

Beavers William N.1,Monteith Andrew J.1,Amarnath Venkataraman1,Mernaugh Raymond L.2,Roberts L. Jackson34,Chazin Walter J.2564,Davies Sean S.364ORCID,Skaar Eric P.164

Affiliation:

1. Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

2. Department of Biochemistry, Vanderbilt University, Nashville, Tennessee, USA

3. Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA

4. Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee, USA

5. Department of Chemistry, Vanderbilt University, Nashville, Tennessee, USA

6. Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, USA

Abstract

Despite the ability of the human immune system to generate a plethora of molecules to control Staphylococcus aureus infections, S. aureus is among the pathogens with the greatest impact on human health. One class of host molecules toxic to S. aureus consists of polyunsaturated fatty acids. Here, we investigated the antibacterial properties of arachidonic acid, one of the most abundant polyunsaturated fatty acids in humans, and discovered that the mechanism of toxicity against S. aureus proceeds through lipid peroxidation. A better understanding of the molecular mechanisms by which the immune system kills S. aureus , and by which S. aureus avoids host killing, will enable the optimal design of therapeutics that complement the ability of the vertebrate immune response to eliminate S. aureus infections.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

American Heart Association

HHS | NIH | National Heart, Lung, and Blood Institute

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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