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Monoterpenoid Geraniol Improves Anti-mycobacterial Drug Efficiency by Interfering with Lipidome and Virulence of Mycobacteria

Author(s):

Sharda Sharma, Saif Hameed and Zeeshan Fatima*   Pages 1 - 19 ( 19 )

Abstract:


Background: Tuberculosis (TB) remains a global infectious disorder for which efficient therapeutics are elusive. Nature is a source of novel pharmacologically active compounds with many potential drugs being derived directly or indirectly from plants, microorganisms and marine organisms.

Objective: The present study aimed to elucidate the antimycobacterial potential of Geraniol (Ger), a monoterpene alcohol, against Mycobacterium tuberculosis (MTB), which is the causative agent of TB.

Methods: Drug susceptibilities were performed by broth microdilution and REMA method. Disrupted membrane integrity was studied by membrane permeability assay and PI uptake. Cell surface phenotypes were studied by colony morphology, sliding motility and cell sedimentation rate. Lipidome profile was demonstrated by thin layer chromatography and liquid chromatography electrospray ionization mass spectrometry. Amendment in iron homeostasis was assessed by using iron chelator ferrozine and ferroxidase assay while genotoxicity was estimated with EtBr and DAPI staining. Biofilm formation was measured by staining, dry mass and metabolic activity using MTT. Cell adherence was examined microscopically and spectrophotometrically.

Results: We found the antimycobacterial activity of Ger to be 250µg/ml against MTB and explored that Ger leads to enhanced drug susceptibilities of most common anti-TB drugs. Underlying mechanisms revealed impaired cell surface phenotypes. Lipidomics analysis exposed profound decrement of mycolic acids, phosphatidylinositol mannosides and triacylglycerides which are crucial for MTB pathogenicity. We further explored that Ger impairs iron homeostasis and leads to genotoxic stress. Moreover, Ger inhibited the potential virulence attributes such as biofilm formation and cell adherence to both polystyrene surface and human oral epithelial cells. Finally, we have validated all the disrupted phenotypes by RT-PCR which showed good correlation with the biochemical assays.

Conclusion: Taken together, the current study demonstrates the antimycobacterial mechanisms of Ger, which may be exploited as an effective candidate of pharmacological interest.

Keywords:

Mycobacterium, Anti-TB drugs, Geraniol, Membrane, Lipidome, Biofilm

Affiliation:

Amity Institute of Biotechnology, Amity University Haryana, Gurgugram (Manesar)-122413, Amity Institute of Biotechnology, Amity University Haryana, Gurgugram (Manesar)-122413, Amity Institute of Biotechnology, Amity University Haryana, Gurgugram (Manesar)-122413



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