Elucidating the antimycobacterial mechanism of action of ciprofloxacin using metabolomics

• DOI: 10.20944/preprints202104.0443.v1
• Publication Date: 2021-04-16T11:51:03Z
• Authors: Kirsten Elke Knoll; Zander Lindeque; Adeniji Ayodele A...; Carel Oosthuizen; Namrita Lall; Du T. Loots
• Keywords: Antimycobacterial; Metabolic pathway; Mechanism of Action; Mode of Action; Purine metabolism

In the interest of developing more effective and safer anti-Tuberculosis treatment, we aimed for a better understanding antimycobacterial action ciprofloxacin against Mycobacterium tuberculosis (Mtb). We used GCxGC-TOF-MS well described metabolomics statistical approaches, to investigate compare metabolic profiles Mtb in presence absence drug. The metabolites that best describe differences between compared groups were identified as markers characterizing changes induced by ciprofloxacin. Malic acid was ranked most significantly altered metabolite marker ciprofloxacin, indicative an inhibition tricarboxylic (TCA) glyoxylate cycle Mtb. fatty acid, myo-inositol triacylglycerol metabolism seen this group, supports previous observations on cell wall. Furthermore, pentose phosphate intermediates, glycerol markers, glucose accumulation, reduction glucogenic amino acids specifically, indicates flux towards DNA (as wall) repair, also supporting findings damage caused This study further provides insights useful designing network whole-system strategies identification possible modes actions various drugs possibly adaptations resulting resistance.