Exogenous metabolite feeding on altering antibiotic susceptibility in Gram-negative bacteria through metabolic modulation: A review

Chung, Wan Yean and Zhu, Yan and Mahamad Maifiah, Mohd Hafidz and Hawala Shivashekaregowda, Naveen Kumar and Wong, Eng Hwa and Abdul Rahim, Nusaibah (2022) Exogenous metabolite feeding on altering antibiotic susceptibility in Gram-negative bacteria through metabolic modulation: A review. Metabolomics, 18 (7). ISSN 1573-3882, DOI https://doi.org/10.1007/s11306-022-01903-w.

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Background The rise of antimicrobial resistance at an alarming rate is outpacing the development of new antibiotics. The worrisome trends of multidrug-resistant Gram-negative bacteria have enormously diminished existing antibiotic activity. Antibiotic treatments may inhibit bacterial growth or lead to induce bacterial cell death through disruption of bacterial metabolism directly or indirectly. In light of this, it is imperative to have a thorough understanding of the relationship of bacterial metabolism with antimicrobial activity and leverage the underlying principle towards development of novel and effective antimicrobial therapies. Objective Herein, we explore studies on metabolic analyses of Gram-negative pathogens upon antibiotic treatment. Metabolomic studies revealed that antibiotic therapy caused changes of metabolites abundance and perturbed the bacterial metabolism. Following this line of thought, addition of exogenous metabolite has been employed in in vitro, in vivo and in silico studies to activate the bacterial metabolism and thus potentiate the antibiotic activity. Key scientific concepts of review Exogenous metabolites were discovered to cause metabolic modulation through activation of central carbon metabolism and cellular respiration, stimulation of proton motive force, increase of membrane potential, improvement of host immune protection, alteration of gut microbiome, and eventually facilitating antibiotic killing. The use of metabolites as antimicrobial adjuvants may be a promising approach in the fight against multidrug-resistant pathogens.

Item Type: Article
Funders: Fundamental Research Grant Scheme, Ministry of Higher Education, Malaysia (Grant No: FRGS/1/2019/SKK11/TAYLOR/03/1)
Uncontrolled Keywords: Antimicrobial resistance; Metabolism; Antibiotic susceptibility; Metabolic modulation; Gram-negative bacteria
Subjects: R Medicine > RK Dentistry
Divisions: Faculty of Pharmacy > Department of Clinical Pharmacy and Pharmacy Practice
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 20 Oct 2023 01:17
Last Modified: 20 Oct 2023 01:17
URI: http://eprints.um.edu.my/id/eprint/41872

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