Anti-staphylococcal fatty acids: mode of action, bacterial resistance and implications for therapeutic application
File(s)
Published version
Author(s)
Douglas, Edward JA
Palk, Nathanael
Rudolph, Emily R
Laabei, Maisem
Type
Journal Article
Abstract
Novel strategies to counter multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus are urgently required. The antimicrobial properties of fatty acids (FAs) have long been recognized and offer significant promise as viable alternatives to, or potentiators of, conventional antibiotics. In this review, we examine the interplay between FAs and S. aureus, specifically detailing the underlying molecular mechanisms responsible for FA-mediated inhibition and the counteracting staphylococcal systems evolved to withstand FA onslaught. Finally, we present an update on the recent therapeutic FA applications to combat S. aureus infection, either as a monotherapy or in combination with antibiotics or host-derived antimicrobial peptides. Given the frequency of interaction between FAs and S. aureus during host colonization and infection, understanding FA mode of action and deciphering S. aureus FA resistance strategies are central in rationally designing future anti-staphylococcal FAs and FA-combination therapies.
Date Issued
2025-05-22
Date Acceptance
2025-04-29
Citation
Microbiology, 2025, 171 (5)
ISSN
1350-0872
Publisher
Microbiology Society
Journal / Book Title
Microbiology
Volume
171
Issue
5
Copyright Statement
© 2025 The Authors This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
License URL
Identifier
10.1099/mic.0.001563
Subjects
fatty acids
mode of action
resistance mechanisms
Staphylococcus aureus
therapeutics. Abbreviations: AD, atopic dermatitis
AMP, antimicrobial peptide
CC, clonal complex
COX, cyclooxygenase
DSF, diffusible signal factor
7,10-EODA, 7,10-epoxyoctadeca-7,9-dienoic acid
EPS, extracellular polymeric substance
ETC, electron transport chain
exoFA, exogenous FA
FA, fatty acid
FAK, FA kinase
FAME, FA-modifying enzyme
GML, glycerol monolaurate
2-HDA, 2-hexadecenoic acid
HFD-P, polyunsaturated high-fat diet
HFD-S, saturated high-fat diet
IsdA, iron-regulated surface determinant protein A
LAM, lauric acid monoester
LCFAs, long-chain FAs
LCP, LytR-CpsA-Psr
LTA, lipoteichoic acid
MDR, multidrug resistant
2M,6-ODA, (6Z)-(±)-2-methoxy-6-octadecenoic acid
MRSA, methicillin-resistant S. aureus
MspA, membrane-stabilizing protein A
MSSA, methicillin-susceptible S. aureus
MVs, membrane vesicles
OhyA, oleate hydratase
PG, phosphatidylglycerol
PGN, peptidoglycan
PMF, proton motive force
PUFA, polyunsaturated FA
RL, rhamnolipid
ROS, reactive oxygen species
SCFA, short-chain FA
sFAs, saturated FAs
STX, staphyloxanthin
TPP+, tetraphenylphosphonium ion
T7SS, type 7 secretion system
uFAs, unsaturated FAs
WTA, wall teichoic acid
Publication Status
Published
Article Number
001563
Date Publish Online
2025-05-22