Wan Yean Chung1, Yan Zhu2, Mohd Hafidz Mahamad Maifiah3, Naveen Kumar Hawala Shivashekaregowda4, Eng Hwa Wong5, Nusaibah Abdul Rahim6. 1. School of Pharmacy, Taylor's University, 47500, Subang Jaya, Selangor, Malaysia. 2. Biomedicine Discovery Institute, Infection and Immunity Program, Department of Microbiology, Monash University, 3800, Victoria, Australia. 3. International Institute for Halal Research and Training (INHART), International Islamic University Malaysia (IIUM), 53100, Jalan Gombak, Selangor, Malaysia. 4. Center for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health and Medical Sciences, Taylor's University, 47500, Subang Jaya, Selangor, Malaysia. 5. School of Medicine, Taylor's University, 47500, Subang Jaya, Selangor, Malaysia. enghwa.wong@taylors.edu.my. 6. Faculty of Pharmacy, University of Malaya, 50603, Kuala Lumpur, Malaysia. nusaibah.abdulrahim@um.edu.my.
Abstract
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.
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.
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