Diversity of fatty acid susceptibility among clinical isolates of Staphylococcus aureus and its role in membrane potential
Abstract
Staphylococcus aureus colonizes human skin, nasal cavity, and oral mucosa and causes opportunistic infections. Host-derived fatty acids exhibit antibacterial activity against S. aureus, but the diversity and determinants of fatty acid susceptibility among clinical isolates remain unclear. Here, we evaluated seven C14-C18 fatty acids selected from a physiologically relevant range of host-associated lipids. Linoleic acid (LA), palmitoleic acid (POA), and γ-linolenic acid (GLA) demonstrated significant antibacterial activity. We then analyzed LA and POA susceptibility in 253 clinical isolates. LA minimum inhibitory concentrations (MICs) ranged widely from 18.75 to 1,200 μM, whereas POA MICs clustered between 37.5 and 150 μM. Low-LA-susceptibility strains showed higher baseline membrane potential-associated signals and weaker LA-induced depolarization. Anaerobic culture and srrA inactivation reduced both of these signals and LA MICs. These findings indicate that membrane potential contributes to the heterogeneity of LA susceptibility and provide insight into host fatty acid-mediated control of S. aureus.
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BibTeX
@article{asada2026diversity,
title = {{Diversity of fatty acid susceptibility among clinical isolates of Staphylococcus aureus and its role in membrane potential}},
author = {Yasuyuki Asada and Saki Nishihama and Miki Kawada-Matsuo and Keijuro Ohdan and Tomonao Aikawa and Souichi Yanamoto and Hitoshi Komatsuzawa},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117798},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03179-2},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Diversity of fatty acid susceptibility among clinical isolates of Staphylococcus aureus and its role in membrane potential
AU - Yasuyuki Asada
AU - Saki Nishihama
AU - Miki Kawada-Matsuo
AU - Keijuro Ohdan
AU - Tomonao Aikawa
AU - Souichi Yanamoto
AU - Hitoshi Komatsuzawa
PY - 2026
DA - 2026/10/08
JO - iScience
DO - 10.1016/j.isci.2026.117798
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03179-2
AB - Staphylococcus aureus colonizes human skin, nasal cavity, and oral mucosa and causes opportunistic infections. Host-derived fatty acids exhibit antibacterial activity against S. aureus, but the diversity and determinants of fatty acid susceptibility among clinical isolates remain unclear. Here, we evaluated seven C14-C18 fatty acids selected from a physiologically relevant range of host-associated lipids. Linoleic acid (LA), palmitoleic acid (POA), and γ-linolenic acid (GLA) demonstrated significant antibacterial activity. We then analyzed LA and POA susceptibility in 253 clinical isolates. LA minimum inhibitory concentrations (MICs) ranged widely from 18.75 to 1,200 μM, whereas POA MICs clustered between 37.5 and 150 μM. Low-LA-susceptibility strains showed higher baseline membrane potential-associated signals and weaker LA-induced depolarization. Anaerobic culture and srrA inactivation reduced both of these signals and LA MICs. These findings indicate that membrane potential contributes to the heterogeneity of LA susceptibility and provide insight into host fatty acid-mediated control of S. aureus.
SN - 2589-0042
ER -