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...

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Main Authors:	Mahamad Maifiah, Mohd Hafidz, Cheah, Soon-Ee, Johnson, Matthew D., Han, Mei-Ling, Boyce, John D., Thamlikitkul, Visanu, Forrest, Alan, Kaye, Keith S., Hertzog, Paul, Purcell, Anthony W., Song, Jiangning, Velkov, Tony, Creek, Darren J., Li, Jian
Format:	Article
Language:	English
Published:	Springer Nature 2016
Subjects:	QR Microbiology RM Therapeutics. Pharmacology RM300 Drugs and their action
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

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recordtype	eprints
spelling	iium-653782018-08-30T00:32:02Z http://irep.iium.edu.my/65378/ Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii Mahamad Maifiah, Mohd Hafidz Cheah, Soon-Ee Johnson, Matthew D. Han, Mei-Ling Boyce, John D. Thamlikitkul, Visanu Forrest, Alan Kaye, Keith S. Hertzog, Paul Purcell, Anthony W. Song, Jiangning Velkov, Tony Creek, Darren J. Li, Jian QR Microbiology RM Therapeutics. Pharmacology RM300 Drugs and their action 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. Springer Nature 2016 Article PeerReviewed application/pdf en http://irep.iium.edu.my/65378/1/2016_SciRep.pdf 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 https://www.nature.com/articles/srep22287.pdf 10.1038/srep22287
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	QR Microbiology RM Therapeutics. Pharmacology RM300 Drugs and their action
spellingShingle	QR Microbiology RM Therapeutics. Pharmacology RM300 Drugs and their action Mahamad Maifiah, Mohd Hafidz Cheah, Soon-Ee Johnson, Matthew D. Han, Mei-Ling Boyce, John D. Thamlikitkul, Visanu Forrest, Alan Kaye, Keith S. Hertzog, Paul Purcell, Anthony W. Song, Jiangning Velkov, Tony Creek, Darren J. Li, Jian Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii
description	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.
format	Article
author	Mahamad Maifiah, Mohd Hafidz Cheah, Soon-Ee Johnson, Matthew D. Han, Mei-Ling Boyce, John D. Thamlikitkul, Visanu Forrest, Alan Kaye, Keith S. Hertzog, Paul Purcell, Anthony W. Song, Jiangning Velkov, Tony Creek, Darren J. Li, Jian
author_facet	Mahamad Maifiah, Mohd Hafidz Cheah, Soon-Ee Johnson, Matthew D. Han, Mei-Ling Boyce, John D. Thamlikitkul, Visanu Forrest, Alan Kaye, Keith S. Hertzog, Paul Purcell, Anthony W. Song, Jiangning Velkov, Tony Creek, Darren J. Li, Jian
author_sort	Mahamad Maifiah, Mohd Hafidz
title	Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii
title_short	Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii
title_full	Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii
title_fullStr	Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii
title_full_unstemmed	Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii
title_sort	global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant acinetobacter baumannii
publisher	Springer Nature
publishDate	2016
url	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
first_indexed	2023-09-18T21:32:46Z
last_indexed	2023-09-18T21:32:46Z
_version_	1777412620844793856

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

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