Exogenous glutamate potentiates gentamicin to kill multidrug- and carbapenem-resistant <i>Pseudomonas aeruginosa</i> by activating the biosynthesis of unsaturated fatty acids
Antibiotic-resistant <i>Pseudomonas aeruginosa</i> is a major clinical challenge due to limited drug uptake. This study shows that exogenous glutamate restores gentamicin efficacy by reprogramming bacterial metabolism to enhance membrane permeability. The effect is mediated through increased biosynthesis of unsaturated fatty acids, which is further confirmed by oleic acid supplementation. These findings reveal a novel metabolic approach to overcome multidrug and carbapenem resistance, offering a promising adjunct strategy to improve antibiotic treatment outcomes.
Authors
- Wu Yuan (ORCID: https://orcid.org/0000-0001-9405-519X)
- Zhuang‐Gui Chen (ORCID: https://orcid.org/0000-0001-8548-4806)
- Zhen-Yuan Dai
- Pan Li (ORCID: https://orcid.org/0000-0002-2819-4439)
- Lifen Yang (ORCID: https://orcid.org/0000-0002-1888-3775)
- Kai Song (ORCID: https://orcid.org/0000-0002-9500-0200)
- Ying Liang
- H L Lai
Institutions
- Sun Yat-sen University (CN)
- Chinese University of Hong Kong (HK)
- Third Affiliated Hospital of Sun Yat-sen University (CN)
Publication Details
- Journal
- mSystems
- Published
- 2025-10-13
- DOI
- https://doi.org/10.1128/msystems.01234-25
- Primary Topic
- Antibiotic Resistance in Bacteria
- Type
- article
- Field-Weighted Citation Impact
- 0.00