ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
This article is part of the Research TopicBacterial Metabolites: Redefining Strategies to Combat Antimicrobial ResistanceView all 7 articles
Glutamate potentiates susceptibility of Ps. aeruginosa clinical isolates to gentamycin: A new adjuvant hope for an old antibiotic
Provisionally accepted
- 1Suez Canal University, Ismaïlia, Egypt
- 2Assiut University, Asyut, Egypt
- 3University College London, London, United Kingdom
- 4Brunel University London, London, United Kingdom
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Aminoglycosides have long been considered essential agents in Ps. aeruginosa chemotherapy; however, resistance is on the rise. Glutamate is a crucial molecule for all living organisms, serving a fundamental function in various metabolic activities. A deeper comprehension of metabolic flux may facilitate effective therapeutic strategies for the eradication of antibiotic-resistant microorganisms. In this work, we aim to investigate a novel approach of amino acid-antibiotic adjuvant to potentiate activity of existing therapeutics through a low-toxicity adjuvant strategy offering lower risk of unwanted effects. We used 25 Ps. aeruginosa whole-genome sequenced clinical isolates selected from a genomically diverse set of isolates. The effect of glutamate-gentamycin combination on bacterial growth was tested. The effect of gentamycin-glutamate combination on outer membrane permeability was also studied using NPN. GWAS analysis was implemented using Pyseer to investigate genes underlying the observed enhanced effect of glutamate/gentamycin combination on bacterial killing. Among the tested 25 Ps. aeruginosa isolates, fifteen isolates demonstrated enhanced combinatorial effect of the gentamycin-glutamate combination resulting in enhanced bacterial killing effect. Interestingly observed, a set of genes involved in glycerophospholipid metabolism, purine metabolism, and glutamate metabolic pathways were interconnected showing significant differences among the two phenotypic groups using Pyseer. The uptake of fluorophore NPN in the presence of glutamate and two sub-inhibitory concentrations of gentamycin was increased indicating increased membrane permeabilization. This study reports the enhanced antibacterial effect of gentamycin-glutamate combination against Ps. aeruginosa opening doors for novel alternative treatment approaches against drug-resistant bacteria. Metabolic reprogramming offers a promising potential to enhance antibiotic mediated bacterial killing.
Keywords: Antibiotic uptake, Gentamycin, Glutamate, Membrane Permeability, Ps. aeruginosa
Received: 31 Jul 2025; Accepted: 08 Dec 2025.
Copyright: © 2025 Nageeb, Hetta, Frampton and Saunders. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wedad M. Nageeb
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