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<p>According to the recent WHO figures, nearly 23% of the world’s population is infected with tuberculosis. The causative pathogen <i>Mycobacterium tuberculosis</i> (Mtb) primarily resides in the macrophages of host cells and hinders the autophagy mechanism by preventing the fusion of phagolysosomes. This study investigated the intracellular antituberculosis activity of bergapten (TPB1), isolated from <i>Tridax procumbens</i>, in human monocytic leukemia-derived (THP-1) cells, as well as its effects on the molecular expression of autophagy-related genes. The determination of the minimum inhibitory concentration (MIC) of bergapten against <i>Mycobacterium tuberculosis</i> by radiometric BACTEC MGIT (Mycobacteria growth indicator tube) 960 and microbroth dilution methods yielded an identical MIC value of 62.5&#xa0;µg/mL. A molecular dynamics (MD) simulation was conducted to assess the stability of the compound and its induced conformational changes in Autophagy-related gene 5 (ATG5) and Microtubule-associated protein 1B light chain 3 (LC3) under real physiological conditions. A 100 ns simulation conducted using GROMACS (GROningen Machine for Chemical Simulations) revealed binding stability as assessed by root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) parameters. Quantitative analysis of mRNA expression revealed that TPB1 has the potential to enhance autophagy by upregulating LC3 and ATG5 genes. Our findings emphasize the significance of investigating naturally derived compounds for the treatment of <i>Mycobacterium tuberculosis</i> and identifying potential antitubercular candidates for further investigations.</p>

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Probable role of naturally derived bergapten molecule promotes autophagy in Mycobacterium tuberculosis-infected macrophages via PI3K/Akt/mTOR pathway

  • 期刊论文

  • 发表日期：

    2025年10月10日

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  • Jayashri Seetharaman,
  • Sam Ebenezer Rajadas,
  • Vignesh Sounderrajan,
  • Akshaya Priya Raveendran,
  • Reya Rene Philip,
  • Sankari Dharmalingam

摘要

According to the recent WHO figures, nearly 23% of the world’s population is infected with tuberculosis. The causative pathogen Mycobacterium tuberculosis (Mtb) primarily resides in the macrophages of host cells and hinders the autophagy mechanism by preventing the fusion of phagolysosomes. This study investigated the intracellular antituberculosis activity of bergapten (TPB1), isolated from Tridax procumbens, in human monocytic leukemia-derived (THP-1) cells, as well as its effects on the molecular expression of autophagy-related genes. The determination of the minimum inhibitory concentration (MIC) of bergapten against Mycobacterium tuberculosis by radiometric BACTEC MGIT (Mycobacteria growth indicator tube) 960 and microbroth dilution methods yielded an identical MIC value of 62.5 µg/mL. A molecular dynamics (MD) simulation was conducted to assess the stability of the compound and its induced conformational changes in Autophagy-related gene 5 (ATG5) and Microtubule-associated protein 1B light chain 3 (LC3) under real physiological conditions. A 100 ns simulation conducted using GROMACS (GROningen Machine for Chemical Simulations) revealed binding stability as assessed by root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) parameters. Quantitative analysis of mRNA expression revealed that TPB1 has the potential to enhance autophagy by upregulating LC3 and ATG5 genes. Our findings emphasize the significance of investigating naturally derived compounds for the treatment of Mycobacterium tuberculosis and identifying potential antitubercular candidates for further investigations.