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Deciphering the action of polymyxins on pentose phosphate pathway metabolism in Acinetobacter Baumannii: a metabolite-based target towards safe antibiotic treatment

Mohd Kamal, Khairunnisa and Mahamad Maifiah, Mohd Hafidz and Hashim, Yumi Zuhanis Has-Yun and Abdullah Sani, Muhamad Shirwan and Abdul Rahim, Nusaibah (2022) Deciphering the action of polymyxins on pentose phosphate pathway metabolism in Acinetobacter Baumannii: a metabolite-based target towards safe antibiotic treatment. IIUM Journal of Orofacial and Health Sciences, 3 (Supplement 1). p. 9. E-ISSN 2735-0584 (In Press)

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Emergence of Acinetobacter baumannii as multidrug-resistant (MDR) bacteria are a major global threat to the healthcare system, forcing the classic polymyxins to be revisited as the last-line therapy against MDR Gram-negative bacteria including A. baumannii. It exhibits rapid bactericidal activity through ‘self-uptake’ pathway to induce local membrane disturbance, osmotic imbalance which lead to cell death. Nevertheless, polymyxins are limited due to the previously reported nephrotoxicity and ineffective suboptimal concentrations among patients. Bacterial metabolic reaction toward antibiotics has not been well studied with cutting-edge metabolomics. Understanding the metabolome of bacterial cells can potentially open an opportunity for novel effective antibacterial therapy. Previous study indicated that there were significant global metabolic disturbance of A. baumannii induced by polymyxin treatments including D-ribose-5-phosphate, D-erythrose-4-phosphate and D- sedoheptulose-7-phosphate of pentose phosphate pathway (PPP) metabolites, highlighting the potential polymyxin target. Therefore, this study aims to investigate the mechanism of polymyxins action on the PPP metabolism in A. baumannii, employing a targeted metabolomics approach through in vitro static time-kill method and metabolic pathway analysis across different time points at 1 hour and 4 hours. Polymyxin B (2mg/L) induced significant bactericidal effect in A. baumannii as rapid killing was observed after 1 hour treatment. However, the bactericidal activity decreased after the first hour as the bacterial growth significantly increased at 4 hours. The significant bactericidal effect of polymyxin at 1 hour reflects its potential in treating A. baumannii infection and further analyzed through metabolomics study. Through targeted metabolomics, detailed analysis on polymyxins’ activity against A. baumannii at cellular level, specifically for PPP metabolism able to provide a novel insight for alternative strategy in combating MDR bacterial infection.

Item Type: Article (other)
Uncontrolled Keywords: Polymyxins, targeted metabolomics, pentose phosphate pathway, multi-drug resistance
Subjects: Q Science > QD Chemistry
Q Science > QK Botany
Q Science > QR Microbiology
R Medicine > RM Therapeutics. Pharmacology > RM300 Drugs and their action
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button): International Institute for Halal Research and Training (INHART)
Depositing User: Dr Mohd Hafidz Mahamad Maifiah
Date Deposited: 07 Feb 2022 09:51
Last Modified: 07 Feb 2022 09:51
URI: http://irep.iium.edu.my/id/eprint/96568

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