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Background:Novel strategies to overcome Multidrug Resistance (MDR) in Tuberculosis (TB) still remain a concern.Usage of natural compounds nowadays to surmount the ever increasing burden of MDR-TB has shown promising results.Objectives: Previously, we have demonstrated the disruption of cell surface integrity as potential antimycobacterial mechanism of vanillin (Van), a natural food flavouring agent and preservative.This study aimed to gain deeper insights into the causal effects of membrane disruption.Methods: Efflux and passive diffusion assay was performed with substrate EtBr.Changes in lipid profiles were studied by thin layer chromatography and lipase assay.PI uptake was done by fluorescence assay.Colony morphology and cell sedimentation were estimated microscopically and spectrophotometrically respectively. Results:We reveal that membrane disruption leads to enhanced passive diffusion of drug independent of drug efflux activity.We further explored that Van caused alterations in lipid as demonstrated by impaired lipid profile and enhanced lipase activity.Commensurate with our findings, we also observed that Van leads to enhanced PI intake validating the hypothesis.Furthermore, we also uncover additional phenotypes related to membrane disruption.We observed that Van affects colony morphology and showed enhanced cell sedimentation rate depicting fluctuations in lipid composition. Conclusion:Taken together, considering the emerging role of lipids in MDR phenotype, alterations in lipid as demonstrated through this study clearly warrants lipidomics based approach to discover novel targets for anti-TB therapeutics.
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Zeeshan Fatima (2017) studied this question.
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