Panduratin A Induces Autophagy Through AMPK Activation Independent of mTOR Inhibition and Restricts Mycobacterium tuberculosis in Host Macrophages
Issued Date
2025-01-01
Resource Type
ISSN
0950382X
eISSN
13652958
Scopus ID
2-s2.0-105017862458
Pubmed ID
41001742
Journal Title
Molecular Microbiology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecular Microbiology (2025)
Suggested Citation
Lamtha T., Davies-Bolorunduro O.F., Phlaetita S., Kaofai C., Kanjanasirirat P., Khumpanied T., Chabang N., Munyoo B., Tuchinda P., Borwornpinyo S., Jamnongsong S., Sampattavanich S., Palittapongarnpim P., Ponpuak M. Panduratin A Induces Autophagy Through AMPK Activation Independent of mTOR Inhibition and Restricts Mycobacterium tuberculosis in Host Macrophages. Molecular Microbiology (2025). doi:10.1111/mmi.70025 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/112514
Title
Panduratin A Induces Autophagy Through AMPK Activation Independent of mTOR Inhibition and Restricts Mycobacterium tuberculosis in Host Macrophages
Corresponding Author(s)
Other Contributor(s)
Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health burden, especially with the increasing prevalence of drug-resistant strains. There is an urgent need for new therapeutics that act via alternative mechanisms. Autophagy, a vital cell-autonomous defense process, allows macrophages to degrade intracellular pathogens such as Mtb and has gained attention as a potential target for host-directed therapy. In this study, we conducted a high-content imaging screen of herb-derived compounds to identify autophagy inducers in RAW264.7 macrophages. Panduratin A (NPA), a natural compound from Boesenbergia rotunda, was found to potently induce autophagy. NPA promoted autophagic vacuole formation in a dose-dependent fashion at low micromolar levels. Its autophagy-inducing effect was validated using RFP-GFP-LC3 dual fluorescence assays and immunoblotting in the presence of bafilomycin A1. Further mechanistic analysis revealed that NPA activates autophagy through AMPK activation, independent of mTOR inhibition. Importantly, NPA significantly promoted intracellular Mtb clearance and increased colocalization of Mtb with autophagosomes and lysosomes, in a manner dependent on Beclin-1. These findings highlight NPA as a potent enhancer of macrophage antimicrobial responses via autophagy, supporting its potential as a candidate for host-directed adjunctive therapy against TB.