Exploring and Exploiting the Host Cell Autophagy During Mycobacterium Tuberculosis Infection

Overview

Journal Eur J Clin Microbiol Infect Dis

Publisher Springer

Specialties Infectious Diseases
Microbiology

Date 2023 Sep 23

PMID 37740791

Authors

Pavan Kumar Nagdev

Puja Kumari Agnivesh

Arnab Roy

Shashikanta Sau

Nitin Pal Kalia

Affiliations

Soon will be listed here.

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis, is a fatal infectious disease that prevails to be the second leading cause of death from a single infectious agent despite the availability of multiple drugs for treatment. The current treatment regimen involves the combination of several drugs for 6 months that remain ineffective in completely eradicating the infection because of several drawbacks, such as the long duration of treatment and the side effects of drugs causing non-adherence of patients to the treatment regimen. Autophagy is an intracellular degradative process that eliminates pathogens at the early stages of infection. Mycobacterium tuberculosis's unique autophagy-blocking capability makes it challenging to eliminate compared to usual pathogens. The present review discusses recent advances in autophagy-inhibiting factors and mechanisms that could be exploited to identify autophagy-inducing chemotherapeutics that could be used as adjunctive therapy with the existing first-line anti-TB agent to shorten the duration of therapy and enhance cure rates from multidrug-resistant tuberculosis (MDR-TB) and extreme drug-resistant tuberculosis (XDR-TB).

Citing Articles

Advances in Host-Pathogen Interactions in Tuberculosis: Emerging Strategies for Therapeutic Intervention.

Nasiri M, Venketaraman V Int J Mol Sci. 2025; 26(4).

PMID: 40004082 PMC: 11855387. DOI: 10.3390/ijms26041621.

Toward Virulence Inhibition: Beyond Cell Wall.

Kotliarova M, Shumkov M, Goncharenko A Microorganisms. 2025; 13(1).

PMID: 39858789 PMC: 11767696. DOI: 10.3390/microorganisms13010021.

References

Zumla A, Chakaya J, Centis R, DAmbrosio L, Mwaba P, Bates M . Tuberculosis treatment and management--an update on treatment regimens, trials, new drugs, and adjunct therapies. Lancet Respir Med. 2015; 3(3):220-34. DOI: 10.1016/S2213-2600(15)00063-6. View

Rabahi M, da Silva Junior J, Ferreira A, Tannus-Silva D, Conde M . Tuberculosis treatment. J Bras Pneumol. 2018; 43(6):472-486. PMC: 5792048. DOI: 10.1590/S1806-37562016000000388. View

Amano A, Nakagawa I, Yoshimori T . Autophagy in innate immunity against intracellular bacteria. J Biochem. 2006; 140(2):161-6. DOI: 10.1093/jb/mvj162. View

Barnett T, Liebl D, Seymour L, Gillen C, Lim J, LaRock C . The globally disseminated M1T1 clone of group A Streptococcus evades autophagy for intracellular replication. Cell Host Microbe. 2013; 14(6):675-82. PMC: 3918495. DOI: 10.1016/j.chom.2013.11.003. View

Neumann Y, Bruns S, Rohde M, Prajsnar T, Foster S, Schmitz I . Intracellular Staphylococcus aureus eludes selective autophagy by activating a host cell kinase. Autophagy. 2016; 12(11):2069-2084. PMC: 5103350. DOI: 10.1080/15548627.2016.1226732. View

Banaiee N, Kincaid E, Buchwald U, Jacobs Jr W, Ernst J . Potent inhibition of macrophage responses to IFN-gamma by live virulent Mycobacterium tuberculosis is independent of mature mycobacterial lipoproteins but dependent on TLR2. J Immunol. 2006; 176(5):3019-27. DOI: 10.4049/jimmunol.176.5.3019. View

Bafica A, Scanga C, Feng C, Leifer C, Cheever A, Sher A . TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis. J Exp Med. 2005; 202(12):1715-24. PMC: 2212963. DOI: 10.1084/jem.20051782. View

Fratti R, Backer J, Gruenberg J, Corvera S, Deretic V . Role of phosphatidylinositol 3-kinase and Rab5 effectors in phagosomal biogenesis and mycobacterial phagosome maturation arrest. J Cell Biol. 2001; 154(3):631-44. PMC: 2196432. DOI: 10.1083/jcb.200106049. View

Fratti R, Chua J, Vergne I, Deretic V . Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest. Proc Natl Acad Sci U S A. 2003; 100(9):5437-42. PMC: 154363. DOI: 10.1073/pnas.0737613100. View

10.

Flynn J, Chan J . Tuberculosis: latency and reactivation. Infect Immun. 2001; 69(7):4195-201. PMC: 98451. DOI: 10.1128/IAI.69.7.4195-4201.2001. View

11.

Bento C, Empadinhas N, Mendes V . Autophagy in the fight against tuberculosis. DNA Cell Biol. 2015; 34(4):228-42. PMC: 4390021. DOI: 10.1089/dna.2014.2745. View

12.

Mizushima N . Autophagy in protein and organelle turnover. Cold Spring Harb Symp Quant Biol. 2011; 76:397-402. DOI: 10.1101/sqb.2011.76.011023. View

13.

Lystad A, Carlsson S, Simonsen A . Toward the function of mammalian ATG12-ATG5-ATG16L1 complex in autophagy and related processes. Autophagy. 2019; 15(8):1485-1486. PMC: 6613903. DOI: 10.1080/15548627.2019.1618100. View

14.

Itakura E, Kishi-Itakura C, Mizushima N . The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes. Cell. 2012; 151(6):1256-69. DOI: 10.1016/j.cell.2012.11.001. View

15.

Wong D, Bach H, Sun J, Hmama Z, Av-Gay Y . Mycobacterium tuberculosis protein tyrosine phosphatase (PtpA) excludes host vacuolar-H+-ATPase to inhibit phagosome acidification. Proc Natl Acad Sci U S A. 2011; 108(48):19371-6. PMC: 3228452. DOI: 10.1073/pnas.1109201108. View

16.

Bach H, Papavinasasundaram K, Wong D, Hmama Z, Av-Gay Y . Mycobacterium tuberculosis virulence is mediated by PtpA dephosphorylation of human vacuolar protein sorting 33B. Cell Host Microbe. 2008; 3(5):316-22. DOI: 10.1016/j.chom.2008.03.008. View

17.

Liu Y, Wang X, Jiang J, Cao Z, Yang B, Cheng X . Modulation of T cell cytokine production by miR-144* with elevated expression in patients with pulmonary tuberculosis. Mol Immunol. 2011; 48(9-10):1084-90. DOI: 10.1016/j.molimm.2011.02.001. View

18.

Cui J, Li Z, Cui K, Gao Y, Zhang B, Niu J . MicroRNA-20a-3p regulates the host immune response to facilitate the mycobacterium tuberculosis infection by targeting IKKβ/NF-κB pathway. Int Immunopharmacol. 2021; 91:107286. DOI: 10.1016/j.intimp.2020.107286. View

19.

Qu Y, Ding S, Ma Z, Jiang D, Xu X, Zhang Y . MiR-129-3p favors intracellular BCG survival in RAW264.7 cells by inhibiting autophagy via Atg4b. Cell Immunol. 2019; 337:22-32. DOI: 10.1016/j.cellimm.2019.01.004. View

20.

Ouimet M, Koster S, Sakowski E, Ramkhelawon B, van Solingen C, Oldebeken S . Mycobacterium tuberculosis induces the miR-33 locus to reprogram autophagy and host lipid metabolism. Nat Immunol. 2016; 17(6):677-86. PMC: 4873392. DOI: 10.1038/ni.3434. View