Discovering Mushroom Compounds to Fight Tuberculosis: A Multi-Target Approach

Jenn Hoskins
20th June, 2024

Discovering Mushroom Compounds to Fight Tuberculosis: A Multi-Target Approach

Image Source: Natural Science News, 2024

Key Findings

  • The study from Dayananda Sagar College of Engineering focuses on identifying new drug targets in Mycobacterium tuberculosis (Mtb) to combat tuberculosis (TB)
  • Researchers targeted essential proteins in the Biotin biosynthesis and Lipoarabinomannan (LAM) pathways of Mtb
  • Bioactive compounds from mushrooms were tested for their potential as anti-TB drugs, with Benz[e]azulene showing promising results
Mycobacterium tuberculosis (Mtb) is a pathogen responsible for causing tuberculosis (TB), a disease with one of the highest mortality rates globally. Tackling TB requires novel therapeutic strategies due to the rising incidence of drug-resistant strains. A recent study from Dayananda Sagar College of Engineering aims to identify and prioritize new drug targets within Mtb, focusing on essential proteins in the Biotin biosynthesis and Lipoarabinomannan (LAM) pathways. This study also investigates the potential of bioactive compounds from mushrooms as prospective anti-TB drugs[1]. The researchers selected crucial proteins such as biotin synthase (bioB) and alpha-(1->6)-mannopyranosyltransferase A (mptA), among others, as drug targets. Proteins without known structures were modeled and validated using bioinformatics tools. The study then explored the interaction of these targets with naturally occurring lead molecules from mushrooms like Agaricus bisporus, Pleurotus djamor, and Hypsizygus ulmarius. Gas Chromatography-Mass Spectrometry (GC-MS) identified 15 bioactive compounds in the methanolic extracts of these mushrooms. Four compounds were chosen based on their drug-likeness and pharmacokinetic properties for molecular docking analysis. Benz[e]azulene from Pleurotus djamor demonstrated a good binding affinity with a score of -9.036 kcal/mol against nuoM (NADH quinone oxidoreductase subunit M), suggesting its potential as an anti-TB candidate. The stability of this complex was validated using Molecular Dynamics (MD) simulations, and the binding free energy was calculated using MM-GBSA analysis. Previous studies have shown that methanolic extracts of mushrooms possess significant antioxidant activities, which could contribute to their therapeutic potential. For instance, extracts from Agaricus bisporus, Hypsizygus ulmarius, and Calocybe indica displayed moderate to excellent antioxidant properties, including free radical scavenging and metal chelating activities[2]. This antioxidant potential might play a role in enhancing the efficacy of mushroom-derived compounds against Mtb. Additionally, the electrostatic interactions between small molecules and their receptors are crucial for molecular recognition and binding affinity. Understanding these interactions can help in optimizing drug design. A study developed a tool to calculate and visualize the electrostatic complementarity (EC) of protein-ligand complexes, which could be applied to predict and improve the binding of mushroom-derived compounds to Mtb proteins[3]. This tool can provide insights into how modifications in these compounds might enhance their efficacy against TB. Moreover, the RDRio genotype of Mtb has been associated with multidrug-resistant TB (MDR-TB), emphasizing the need for new therapeutic approaches. A study investigating the frequency of M. tuberculosis RDRio in Minas Gerais, Brazil, found a significant association between this genotype and MDR-TB[4]. The identification of effective compounds from mushrooms could provide an alternative treatment option for MDR-TB patients. Lastly, a method for detecting antibacterial compounds in mushrooms, including those from Agaricus bisporus, has been developed. This method uses ultra-high performance liquid chromatography triple quadrupole tandem mass spectrometry (UHPLC-MS/MS) and could be applied to ensure the purity and efficacy of mushroom-derived anti-TB compounds[5]. In conclusion, the study from Dayananda Sagar College of Engineering highlights the potential of bioactive compounds from mushrooms in combating TB. By targeting essential proteins in Mtb and leveraging the antioxidant properties of mushrooms, this research paves the way for developing new, effective treatments for TB, including drug-resistant strains.



Main Study

1) Screening of bioactive compounds from selected mushroom species against putative drug targets in Mycobacterium tuberculosis: a multi-target approach.

Published 19th June, 2024

Related Studies

2) Antioxidant properties and electrochemical behavior of cultivated commercial Indian edible mushrooms.

3) Electrostatic Complementarity as a Fast and Effective Tool to Optimize Binding and Selectivity of Protein-Ligand Complexes.

4) Frequency of the Mycobacterium tuberculosis RDRio genotype and its association with multidrug-resistant tuberculosis.

5) Simultaneous determination of 45 antibacterial compounds in mushrooms - Agaricus bisporus by ultra-high performance liquid chromatography-tandem mass spectrometry.

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