Metabolomics of colistin methanesulfonate treated Mycobacterium tuberculosis

Show simple item record Koen, Nadia Van Breda, Shane Vontelin Loots, Du Toit 2018-08-20T11:21:56Z 2018-07
dc.description.abstract Over the past 5 years, there has been a renewed interest in finding new compounds with anti-TB action. Colistin methanesulfonate or polymyxin E, is a possible anti-TB drug candidate, which may in future be used either alone or in combination to the current 6 month “directly observed treatment short-course” (DOTS) regimen. However its mechanism of action has to date not yet been fully explored, and only described from a histological and genomics perspective. Considering this, we used a GCxGC-TOFMS metabolomics approach and identified those metabolite markers characterising Mycobacterium tuberculosis (Mtb) cultured in the presence of colistin methanesulfonate, in order to better understand or confirm its mechanism of action. The metabolite markers identified indicated a flux in the metabolism of the colistin methanesulfonate treated Mtb towards fatty acid synthesis and cell wall repair, confirming previous reports that colistin acts by disrupting the cell wall of mycobacteria. Accompanying this, is a subsequently elevated glucose uptake, since the latter now serves as the primary energy substrate for the upregulated glyoxylate cycle, and additionally as a precursor for further fatty acid synthesis via the glycerolipid metabolic pathway. Furthermore, the elevated concentrations of those metabolites associated with pentose phosphate, valine, threonine, and pentanediol metabolism, also confirms a shift towards glucose utilization for energy production, in the colistin methanesulfonate treated Mtb. en_ZA
dc.description.department Internal Medicine en_ZA
dc.description.embargo 2019-07-01
dc.description.librarian hj2018 en_ZA
dc.description.sponsorship Prof. Anton Stoltz and Prof. Ed Nardell are specifically thanked for their funding towards the cell cultures. The North West University is thanked for financial assistance of the research which forms part of a master's study. en_ZA
dc.description.uri en_ZA
dc.identifier.citation Koen, N., Van Breda, S.V. & Loots, D.T. 2018, 'Metabolomics of colistin methanesulfonate treated Mycobacterium tuberculosis', Tuberculosis, vol. 111, pp. 154-160. en_ZA
dc.identifier.issn 1472-9792 (print)
dc.identifier.issn 1873-281X (online)
dc.identifier.other 10.1016/
dc.language.iso en en_ZA
dc.publisher Elsevier en_ZA
dc.rights © 2018 Elsevier Ltd. All rights reserved. Notice : this is the author’s version of a work that was accepted for publication in Tuberculosis. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. A definitive version was subsequently published in Tuberculosis, vol. 111, pp. 154-160, 2018. doi : 10.1016/ en_ZA
dc.subject Mycobacterium tuberculosis (MTB) en_ZA
dc.subject Antibiotics en_ZA
dc.subject Treatment en_ZA
dc.subject Metabolomics en_ZA
dc.subject Tuberculosis (TB) en_ZA
dc.subject Colistin methanesulfonate en_ZA
dc.subject Polymyxin E en_ZA
dc.title Metabolomics of colistin methanesulfonate treated Mycobacterium tuberculosis en_ZA
dc.type Postprint Article en_ZA

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