Regulatory Mechanisms of Autophagy-Targeted Antimicrobial Therapeutics Against Mycobacterial Infection
- PMID: 33828998
- PMCID: PMC8019938
- DOI: 10.3389/fcimb.2021.633360
Regulatory Mechanisms of Autophagy-Targeted Antimicrobial Therapeutics Against Mycobacterial Infection
Abstract
Mycobacterium tuberculosis (Mtb) is an intracellular pathogen causing human tuberculosis, an infectious disease that still remains as a global health problem. Autophagy, a lysosomal degradative process, has emerged as a critical pathway to restrict intracellular Mtb growth through enhancement of phagosomal maturation. Indeed, several autophagy-modulating agents show promise as host-directed therapeutics for Mtb infection. In this Review, we discuss recent progress in our understanding the molecular mechanisms underlying the action of autophagy-modulating agents to overcome the immune escape strategies mediated by Mtb. The factors and pathways that govern such mechanisms include adenosine 5'-monophosphate-activated protein kinase, Akt/mammalian TOR kinase, Wnt signaling, transcription factor EB, cathelicidins, inflammation, endoplasmic reticulum stress, and autophagy-related genes. A further understanding of these mechanisms will facilitate the development of host-directed therapies against tuberculosis as well as infections with other intracellular bacteria targeted by autophagic degradation.
Keywords: AMPK; Mycobacterium tuberculosis; autophagy; host-directed therapeutics; mTOR.
Copyright © 2021 Silwal, Paik, Kim, Yoshimori and Jo.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/8019938/bin/fcimb-11-633360-g001.gif)
Similar articles
-
An Interplay Between Autophagy and Immunometabolism for Host Defense Against Mycobacterial Infection.Front Immunol. 2020 Nov 12;11:603951. doi: 10.3389/fimmu.2020.603951. eCollection 2020. Front Immunol. 2020. PMID: 33262773 Free PMC article. Review.
-
Host-directed therapy with amiodarone in preclinical models restricts mycobacterial infection and enhances autophagy.Microbiol Spectr. 2024 Aug 6;12(8):e0016724. doi: 10.1128/spectrum.00167-24. Epub 2024 Jun 25. Microbiol Spectr. 2024. PMID: 38916320 Free PMC article.
-
Autophagy: A new strategy for host-directed therapy of tuberculosis.Virulence. 2019 Dec;10(1):448-459. doi: 10.1080/21505594.2018.1536598. Epub 2018 Nov 2. Virulence. 2019. PMID: 30322337 Free PMC article. Review.
-
MIR144* inhibits antimicrobial responses against Mycobacterium tuberculosis in human monocytes and macrophages by targeting the autophagy protein DRAM2.Autophagy. 2017 Feb;13(2):423-441. doi: 10.1080/15548627.2016.1241922. Epub 2016 Oct 20. Autophagy. 2017. PMID: 27764573 Free PMC article.
-
Ursolic Acid Promotes Autophagy by Inhibiting Akt/mTOR and TNF-α/TNFR1 Signaling Pathways to Alleviate Pyroptosis and Necroptosis in Mycobacterium tuberculosis-Infected Macrophages.Inflammation. 2023 Oct;46(5):1749-1763. doi: 10.1007/s10753-023-01839-w. Epub 2023 May 22. Inflammation. 2023. PMID: 37212951
Cited by
-
GSK2656157, a PERK Inhibitor, Alleviates Pyroptosis of Macrophages Induced by Mycobacterium Bacillus Calmette-Guerin Infection.Int J Mol Sci. 2023 Nov 12;24(22):16239. doi: 10.3390/ijms242216239. Int J Mol Sci. 2023. PMID: 38003429 Free PMC article.
-
Itaconate family-based host-directed therapeutics for infections.Front Immunol. 2023 May 16;14:1203756. doi: 10.3389/fimmu.2023.1203756. eCollection 2023. Front Immunol. 2023. PMID: 37261340 Free PMC article. Review.
-
Dimethyl itaconate is effective in host-directed antimicrobial responses against mycobacterial infections through multifaceted innate immune pathways.Cell Biosci. 2023 Mar 8;13(1):49. doi: 10.1186/s13578-023-00992-x. Cell Biosci. 2023. PMID: 36882813 Free PMC article.
-
Mycobacterium avium subsp. paratuberculosis antigens induce cellular immune responses in cattle without causing reactivity to tuberculin in the tuberculosis skin test.Front Immunol. 2023 Jan 18;13:1087015. doi: 10.3389/fimmu.2022.1087015. eCollection 2022. Front Immunol. 2023. PMID: 36741398 Free PMC article.
-
Pathogenicity and virulence of Mycobacterium tuberculosis.Virulence. 2023 Dec;14(1):2150449. doi: 10.1080/21505594.2022.2150449. Virulence. 2023. PMID: 36419223 Free PMC article. Review.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous