Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii
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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2016
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| Subjects: | |
| Online Access: | http://irep.iium.edu.my/65378/ http://irep.iium.edu.my/65378/ http://irep.iium.edu.my/65378/ http://irep.iium.edu.my/65378/1/2016_SciRep.pdf |
| Summary: | 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. |
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