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Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii

Authors :
Maifiah, MHM
Cheah, S-E
Johnson, MD
Han, M-L
Boyce, JD
Thamlikitkul, V
Forrest, A
Kaye, KS
Hertzog, P
Purcell, AW
Song, J
Velkov, T
Creek, DJ
Li, J
Maifiah, MHM
Cheah, S-E
Johnson, MD
Han, M-L
Boyce, JD
Thamlikitkul, V
Forrest, A
Kaye, KS
Hertzog, P
Purcell, AW
Song, J
Velkov, T
Creek, DJ
Li, J
Publication Year :
2016

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 polymyxin-susceptible 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 polymyxin-resistant 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.

Details

Database :
OAIster
Publication Type :
Electronic Resource
Accession number :
edsoai.on1315723449
Document Type :
Electronic Resource