Mahamad Maifiah, Mohd Hafidz and Cheah, Soon-Ee and Johnson, Matthew D. and Han, Mei-Ling and Boyce, John D. and Thamlikitkul, Visanu and Forrest, Alan and Kaye, Keith S. and Hertzog, Paul and Purcell, Anthony W. and Song, Jiangning and Velkov, Tony and Creek, Darren J. and Li, Jian (2016) Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii. Scientific Reports, 6. pp. 1-17. ISSN 2045-2322
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Abstract
Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxinsusceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03–149.1 (polymyxin-susceptible) and 03–149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxinresistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii.
| Item Type: | Article (Journal) |
|---|---|
| Additional Information: | 8219/65378 |
| Uncontrolled Keywords: | antiinfective, agentlipid, Apolymyxin |
| Subjects: | Q Science > QR Microbiology R Medicine > RM Therapeutics. Pharmacology 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: | 30 Aug 2018 08:32 |
| Last Modified: | 30 Aug 2018 08:32 |
| URI: | http://irep.iium.edu.my/id/eprint/65378 |
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