Arachidonic Acid Kills Staphylococcus aureus through a Lipid Peroxidation Mechanism
William N Beavers1, Andrew J Monteith1, Venkataraman Amarnath1
1Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Mbio
|October 3, 2019
Summary
Arachidonic acid (AA) kills Staphylococcus aureus via lipid peroxidation, damaging bacterial macromolecules. Resistance to AA toxicity in a mutant strain increases susceptibility to antibiotics and reduces virulence, highlighting a potential therapeutic target.
Area of Science:
- Microbiology
- Biochemistry
- Immunology
Background:
- Staphylococcus aureus is a significant human pathogen.
- Vertebrates produce antimicrobial compounds, including polyunsaturated fatty acids, to combat bacterial infections.
- Arachidonic acid (AA) is an abundant polyunsaturated fatty acid released during the oxidative burst, known to be toxic to S. aureus.
Purpose of the Study:
- To elucidate the mechanism by which arachidonic acid (AA) exerts toxicity against Staphylococcus aureus.
- To investigate the consequences of S. aureus resistance to AA toxicity.
Main Methods:
- Investigated the mechanism of AA toxicity in S. aureus.
- Utilized a genetically inactivated S. aureus strain (USA300 ΔlcpA mutant) with reduced reactive oxygen species production.
- Assessed the impact of AA resistance on bacterial susceptibility to beta-lactam antibiotics and virulence in a murine infection model.
Main Results:
- Arachidonic acid (AA) kills S. aureus through a lipid peroxidation mechanism, generating reactive electrophiles that modify bacterial macromolecules.
- Antioxidants and the ΔlcpA mutation rescued S. aureus from AA-induced toxicity.
- S. aureus mutants resistant to AA exhibited increased susceptibility to beta-lactam antibiotics and attenuated virulence in vivo.
Conclusions:
- Lipid peroxidation is the mechanism underlying arachidonic acid toxicity to S. aureus.
- Resistance to AA toxicity confers a fitness cost, increasing susceptibility to other host stressors.
- Targeting the lipid peroxidation pathway presents a potential therapeutic strategy against S. aureus infections.
Keywords:
MRSAStaphylococcus aureusarachidonic acidisolevuglandinspathogenesispolyunsaturated fatty acidswall teichoic acidsMore Related Videos
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