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Sci Rep. 2016 Feb 29;6:22287. doi: 10.1038/srep22287.

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

Author information

1
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
2
Department of Microbiology, Faculty of Medicine, Nursing &Health Sciences, Monash University, Clayton, VIC, 3800, Australia.
3
Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
4
UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7569, USA.
5
Detroit Medical Centre and Wayne State University, University Health Centre, Detroit, MI, 48201, USA.
6
Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia.
7
Faculty of Medicine, Nursing &Health Sciences, Monash University, Clayton, VIC, 3800, Australia.
8
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Nursing &Health Sciences, Monash University, Clayton, VIC, 3800, Australia.

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.

PMID:
26924392
PMCID:
PMC4770286
DOI:
10.1038/srep22287
[Indexed for MEDLINE]
Free PMC Article

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