Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics

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dc.contributor.authorKnoll, Kirsten E
dc.contributor.authorLindeque, Zander
dc.contributor.authorAdeniji, Adetomiwa A
dc.contributor.authorOosthuizen, Carel B
dc.contributor.authorLall, Namrita
dc.contributor.authorLoots, Du Toit
dc.date.accessioned2021-11-24T16:42:09Z
dc.date.available2021-11-24T16:42:09Z
dc.date.issued2021-05-28
dc.date.updated2021-07-08T14:23:25Z
dc.description.abstractAbstract: In the interest of developing more effective and safer anti-tuberculosis drugs, we used a GCxGC-TOF-MS metabolomics research approach to investigate and compare the metabolic profiles of Mtb in the presence and absence of ciprofloxacin. The metabolites that best describe the differences between the compared groups were identified as markers characterizing the changes induced by ciprofloxacin. Malic acid was ranked as the most significantly altered metabolite marker induced by ciprofloxacin, indicative of an inhibition of the tricarboxylic acid (TCA) and glyoxylate cycle of Mtb. The altered fatty acid, myo-inositol, and triacylglycerol metabolism seen in this group supports previous observations of ciprofloxacin action on the Mtb cell wall. Furthermore, the altered pentose phosphate intermediates, glycerol metabolism markers, glucose accumulation, as well as the reduction in the glucogenic amino acids specifically, indicate a flux toward DNA (as well as cell wall) repair, also supporting previous findings of DNA damage caused by ciprofloxacin. This study further provides insights useful for designing network whole-system strategies for the identification of possible modes of action of various drugs and possibly adaptations by Mtb resulting in resistanceen_US
dc.identifierdoi: 10.3390/microorganisms9061158
dc.identifier.apacitationKnoll, K. E., Lindeque, Z., Adeniji, A. A., Oosthuizen, C. B., Lall, N., & Loots, D. T. (2021). Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics. <i>Microorganisms</i>, 9(6), 1158. http://hdl.handle.net/11427/35364en_ZA
dc.identifier.chicagocitationKnoll, Kirsten E, Zander Lindeque, Adetomiwa A Adeniji, Carel B Oosthuizen, Namrita Lall, and Du Toit Loots "Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics." <i>Microorganisms</i> 9, 6. (2021): 1158. http://hdl.handle.net/11427/35364en_ZA
dc.identifier.citationKnoll, K.E., Lindeque, Z., Adeniji, A.A., Oosthuizen, C.B., Lall, N. & Loots, D.T. 2021. Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics. <i>Microorganisms.</i> 9(6):1158. http://hdl.handle.net/11427/35364en_ZA
dc.identifier.ris TY - Journal Article AU - Knoll, Kirsten E AU - Lindeque, Zander AU - Adeniji, Adetomiwa A AU - Oosthuizen, Carel B AU - Lall, Namrita AU - Loots, Du Toit AB - Abstract: In the interest of developing more effective and safer anti-tuberculosis drugs, we used a GCxGC-TOF-MS metabolomics research approach to investigate and compare the metabolic profiles of Mtb in the presence and absence of ciprofloxacin. The metabolites that best describe the differences between the compared groups were identified as markers characterizing the changes induced by ciprofloxacin. Malic acid was ranked as the most significantly altered metabolite marker induced by ciprofloxacin, indicative of an inhibition of the tricarboxylic acid (TCA) and glyoxylate cycle of Mtb. The altered fatty acid, myo-inositol, and triacylglycerol metabolism seen in this group supports previous observations of ciprofloxacin action on the Mtb cell wall. Furthermore, the altered pentose phosphate intermediates, glycerol metabolism markers, glucose accumulation, as well as the reduction in the glucogenic amino acids specifically, indicate a flux toward DNA (as well as cell wall) repair, also supporting previous findings of DNA damage caused by ciprofloxacin. This study further provides insights useful for designing network whole-system strategies for the identification of possible modes of action of various drugs and possibly adaptations by Mtb resulting in resistance DA - 2021-05-28 DB - OpenUCT DP - University of Cape Town IS - 6 J1 - Microorganisms LK - https://open.uct.ac.za PY - 2021 T1 - Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics TI - Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics UR - http://hdl.handle.net/11427/35364 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/35364
dc.identifier.vancouvercitationKnoll KE, Lindeque Z, Adeniji AA, Oosthuizen CB, Lall N, Loots DT. Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics. Microorganisms. 2021;9(6):1158. http://hdl.handle.net/11427/35364.en_ZA
dc.language.isoenen_US
dc.publisher.departmentDepartment of Biological Sciencesen_US
dc.publisher.facultyFaculty of Scienceen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceMicroorganismsen_US
dc.source.journalissue6en_US
dc.source.journalvolume9en_US
dc.source.pagination1158en_US
dc.source.urihttps://www.mdpi.com/journal/microorganisms
dc.titleElucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomicsen_US
dc.typeJournal Articleen_US
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