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Exploring and exploiting the host cell autophagy during Mycobacterium tuberculosis infection

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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).

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References

  1. World Health Organization (2021) Global tuberculosis report. Glob tuberkulosis Rep https://doi.org/https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2021

  2. Zumla A, Chakaya J, Centis R, D’Ambrosio L, Mwaba P, Bates M et al (2015) Tuberculosis treatment and management-an update on treatment regimens, trials, new drugs, and adjunct therapies. Lancet Respir Med 3:220–234. https://doi.org/10.1016/S2213-2600(15)00063-6

    Article  PubMed  Google Scholar 

  3. Rabahi MF, Da Silva Júnior JLR, Ferreira ACG, Tannus-Silva DGS, Conde MB (2017) Tuberculosis treatment. J Bras Pneumol 43:472–486. https://doi.org/10.1590/s1806-37562016000000388

    Article  PubMed  PubMed Central  Google Scholar 

  4. Amano A, Nakagawa I, Yoshimori T (2006) Autophagy in innate immunity against intracellular bacteria. J. Biochem 140:161–166. https://doi.org/10.1093/jb/mvj162

    Article  CAS  PubMed  Google Scholar 

  5. Schmid U, Seidel H (2006) Autophagy in innate and adaptive immunity against intracellular pathogens. https://doi.org/10.1007/s00109-005-0014-4

  6. Barnett TC, Liebl D, Seymour LM, Gillen CM, Lim JY, Larock CN et al (2013) The globally disseminated M1T1 clone of group a streptococcus evades autophagy for intracellular replication. Cell Host Microbe 14:675–682. https://doi.org/10.1016/j.chom.2013.11.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Neumann Y, Bruns SA, Rohde M, Prajsnar TK, Foster SJ, Schmitz I (2016) Intracellular Staphylococcus aureus eludes selective autophagy by activating a host cell kinase. Autophagy 12:2069–2084. https://doi.org/10.1080/15548627.2016.1226732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Yang A, Pantoom S, Wu YW (2017) Elucidation of the anti-autophagy mechanism of the Legionella effector RavZ using semisynthetic LC3 proteins. Elife 6:1–23. https://doi.org/10.7554/eLife.23905

    Article  Google Scholar 

  9. Mu C (2009) Macroautophagy in immunity and tolerance:615–620. https://doi.org/10.1111/j.1600-0854.2009.00883.x

  10. Banaiee N, Kincaid EZ, Buchwald U, Jacobs WR, Ernst JD (2006) Potent inhibition of macrophage responses to IFN-γ by live virulent Mycobacterium tuberculosis is independent of mature mycobacterial lipoproteins but dependent on TLR2. J Immunol 176:3019–3027. https://doi.org/10.4049/jimmunol.176.5.3019

    Article  CAS  PubMed  Google Scholar 

  11. Bafica A, Scanga CA, Feng CG, Leifer C, Cheever A, Sher A (2005) TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis. J Exp Med 202:1715–1724. https://doi.org/10.1084/jem.20051782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Armstrong JA, Hart D (1971) Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. J Exp Med 1(134):713–740. https://doi.org/http://rupress.org/jem/article-pdf/134/3/713/1415906/713

    Article  Google Scholar 

  13. Fratti RA, Backer JM, Gruenberg J, Corvera S, Deretic V (2001) Role of phosphatidylinositol 3-kinase and Rab5 effectors in phagosomal biogenesis and mycobacterial phagosome maturation arrest. J Cell Biol 154:631–644. https://doi.org/10.1083/jcb.200106049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Fratti RA, Chua J, Vergne I, Deretic V (2003) Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest. Proc Natl Acad Sci U S A 100:5437–5442. https://doi.org/10.1073/pnas.0737613100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Orme IM, Basaraba RJ (2014) The formation of the granuloma in tuberculosis infection. Semin Immunol 1(26):601–609. https://doi.org/10.1016/J.SMIM.2014.09.009

    Article  Google Scholar 

  16. Ehlers S, Schaible UE (2012) The granuloma in tuberculosis: dynamics of a host-pathogen collusion. Front Immunol 3:1–10. https://doi.org/10.3389/fimmu.2012.00411

    Article  Google Scholar 

  17. Flynn JL, Chan J (2001) Tuberculosis: latency and reactivation. Infect Immun 69:4195–4201. https://doi.org/10.1128/IAI.69.7.4195-4201.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gupta A, Kaul A, Tsolaki AG, Kishore U, Bhakta S (2012) Mycobacterium tuberculosis: immune evasion, latency and reactivation. Immunobiology 1(217):363–374. https://doi.org/10.1016/J.IMBIO.2011.07.008

    Article  Google Scholar 

  19. Mizushima N. A brief history of autophagy from cell biology to physiology and disease. Nat Cell Biol 2018 205 2018 ;20:521–7. https://www.nature.com/articles/s41556-018-0092-5

  20. Bento CF, Empadinhas N, Mendes V (2015) Autophagy in the fight against tuberculosis. DNA Cell Biol. 34:228–242. https://doi.org/10.1089/dna.2014.2745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mizushima N (2011) Autophagy in protein and organelle turnover. Cold Spring Harb Symp Quant Biol 76:397–402. https://doi.org/10.1101/sqb.2011.76.011023

    Article  CAS  PubMed  Google Scholar 

  22. Parzych KR, Klionsky DJ. An overview of autophagy: morphology, mechanism, and regulation. https://home.liebertpub.com/ars;20:46073.doi:https://www.liebertpub.com

  23. Cao W, Li J, Yang K, Cao D (2021) An overview of autophagy: mechanism, regulation and research progress. Bull Cancer 1(108):304–322. https://doi.org/10.1016/J.BULCAN.2020.11.004

    Article  Google Scholar 

  24. Klionsky DJ, Cregg JM, Dunn WA Jr, Emr SD, Sakai Y, Sandoval IV, Sibirny A, Subramani S, Thumm M, Veenhuis M, Ohsumi Y (2003) A unified nomenclature for yeast autophagy-related genes. Dev Cell 5:539–45

  25. Dikic I, Elazar Z (2018) Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol 196(19):349–364. https://doi.org/https://www.nature.com/articles/s41580-018-0003-4

    Article  Google Scholar 

  26. Ohsumi Y (1998) Apg14p and Apg6 / Vps30p form a protein complex essential for autophagy in the yeast. Saccharomyces cerevisiae *. 273:22284–22291

    Google Scholar 

  27. Liang C, Feng P, Ku B, Dotan I, Canaani D, Oh B et al (2006) Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. 8. https://doi.org/10.1038/ncb1426

  28. Proikas-cezanne T, Waddell S, Gaugel A, Frickey T, Lupas A, Nordheim A (2004) WIPI-1 a ( WIPI49 ), a member of the novel 7-bladed WIPI protein family , is aberrantly expressed in human cancer and is linked to starvation-induced autophagy:9314–9325. https://doi.org/10.1038/sj.onc.1208331

  29. Polson HEJ, Lartigue J (2010) De, Rigden DJ, Reedijk M, Clague MJ, Tooze SA, et al. Mammalian Atg18 ( WIPI2 ) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation. 8627. https://doi.org/10.4161/auto.6.4.11863

  30. Mizushima N, Noda T, Yoshimori T, Tanaka Y, Ishii T, George MD, Klionsky DJ, Ohsumi M, Ohsumi Y (1998) A protein conjugation system essential for autophagy. Nature 395:395–398. https://doi.org/10.1038/26506

  31. Mizushima N, Noda T, Ohsumi Y (1999) Apg16p is required for the function of the Apg12p–Apg5p conjugate in the yeast autophagy pathway. EMBO J 18(14):3888–3896. https://doi.org/10.1093/emboj/18.14.3888

  32. Death C, Dikic I (2018) Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol. https://doi.org/10.1038/s41580-018-0003-4

  33. Weidberg H, Shvets E, Shpilka T, Shimron F, Shinder V, Elazar Z LC3 and GATE-16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis. EMBO J 29:1792–1802 https://onlinelibrary.wiley.com

  34. Kirisako T, Baba M, Ishihara N, Miyazawa K, Ohsumi M, Yoshimori T et al (1999) Formation process of autophagosome is traced with Apg8/Aut7p in yeast. J Cell Biol 18(147):435–446 https://doi.org/http://www.jcb.orgdoi:%2010.1083/JCB.147.2.435

    Article  Google Scholar 

  35. Taylor P (2011) a n d e s i o s c i e n c e o n o t d i s t r i b u t e. https://doi.org/10.4161/auto.7.8.15860

  36. Singh P, Subbian S (2018) Harnessing the mTOR pathway for tuberculosis treatment. 9:1–11. https://doi.org/10.3389/fmicb.2018.00070

  37. Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y et al (2009) Nutrient-dependent mTORC1 association with the ULK1 – Atg13 – FIP200 complex required for autophagy. 20:1981–1991. https://doi.org/10.1091/mbc.E08

  38. Ha J, Guan K, Kim J. Dept , of Biochemistry and Molecular Biology , Medical Research Center and Biomedical Dept . of Oral Biochemistry and Molecular Biology , Research Center for Tooth and. Mol. Aspects Med. 2015; https://doi.org/10.1016/j.mam.2015.08.002

  39. Nascimbeni AC, Giordano F, Codogno P, Morel E, Dupont N, Grasso D et al (2018) ER – plasma membrane contact sites contribute to autophagosome biogenesis by regulation of local PI 3 P synthesis. 36:2018–2033. https://doi.org/10.15252/embj.201797006

  40. Strong LM, Chang C, Riley JF, Boecker CA, Flower TG, Buffalo CZ, Ren X, Stavoe AK, Holzbaur EL, Hurley JH (2021) Structural basis for membrane recruitment of ATG16L1 by WIPI2 in autophagy. Elife 10:e70372. https://doi.org/10.7554/eLife.70372

  41. Lystad AH, Carlsson SR, Simonsen A, Carlsson SR (2019) Toward the function of mammalian ATG12 – ATG5- ATG16L1 complex in autophagy and related processes and related processes. Autophagy 15:1485–1486. https://doi.org/10.1080/15548627.2019.1618100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Furuta N, Fujita N, Noda T, Yoshimori T, Amano A (2010) Combinational soluble N -ethylmaleimide-sensitive factor attachment protein receptor proteins VAMP8 and Vti1b mediate fusion of antimicrobial and canonical autophagosomes with lysosomes. 21:1001–1010. https://doi.org/10.1091/mbc.E09

  43. Taylor P Syntaxin 17:4–7. https://doi.org/10.4161/auto.24109

  44. Itakura E, Kishi-itakura C, Mizushima N (2012) The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes / lysosomes. Cell 151:1256–1269. https://doi.org/10.1016/j.cell.2012.11.001

    Article  CAS  PubMed  Google Scholar 

  45. Morelli E, Ginefra P, Mastrodonato V, Galina V, Rusten TE, Bilder D et al (2014) Multiple functions of the SNARE protein Snap29 in autophagy , endocytic , and exocytic trafficking during epithelial formation in Drosophila Multiple functions of the SNARE protein Snap29 in autophagy , endocytic , and exocytic trafficking during epithe. 8627. https://doi.org/10.4161/15548627.2014.981913

  46. Hyttinen JMT, Niittykoski M, Salminen A, Kaarniranta K (2013) Biochimica et Biophysica Acta Maturation of autophagosomes and endosomes : a key role for Rab7. BBA - Mol Cell Res 1833:503–510. https://doi.org/10.1016/j.bbamcr.2012.11.018

    Article  CAS  Google Scholar 

  47. Armstrong JA, Hart PD (1971) Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. J Exp Med 134(3):713–740. https://doi.org/10.1084/jem.134.3.713

  48. Mahairas GG, Sabo PJ, Hickey MJ, Singh DC, Stover CK (1996) Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis 178:1274–1282

    CAS  Google Scholar 

  49. Peng X, Sun J (2015) Mechanism of ESAT-6 membrane interaction and its roles in pathogenesis of Mycobacterium tuberculosis. Toxicon. https://doi.org/10.1016/j.toxicon.2015.10.003

  50. Essafi M. i v o r l a n o v l. 2018. https://doi.org/10.3389/fcimb.2018.00327

  51. Yang S, Li F, Jia S, Zhang K, Jiang W, Shang Y et al (2015) Early secreted antigen ESAT-6 of Mycobacterium tuberculosis promotes apoptosis of macrophages via targeting the microRNA155 – SOCS1 interaction. 400042:1276–1288. https://doi.org/10.1159/000373950

  52. Puri RV, Reddy PV, Tyagi AK (2013) Secreted acid phosphatase ( SapM ) of Mycobacterium tuberculosis is indispensable for arresting phagosomal maturation and growth of the pathogen in guinea pig tissues. 8. https://doi.org/10.1371/journal.pone.0070514

  53. Chauhan P, Reddy PV, Singh R, Jaisinghani N, Gandotra S (2013) Secretory phosphatases deficient mutant of Mycobacterium tuberculosis imparts protection at the primary site of infection in guinea pigs. 8:1–15. https://doi.org/10.1371/journal.pone.0077930

  54. Festjens N, Bogaert P, Batni A, Houthuys E, Plets E, Vanderschaeghe D et al (2011) Disruption of the SapM locus in Mycobacterium bovis BCG improves its protective efficacy as a vaccine against M. tuberculosis:222–234. https://doi.org/10.1002/emmm.201000125

  55. Fernandez-soto P, Bruce AJE, Fielding AJ, Cavet JS, Tabernero L (2019) Mechanism of catalysis and inhibition of Mycobacterium tuberculosis SapM , implications for the development of novel antivirulence drugs. Sci Rep:1–14. https://doi.org/10.1038/s41598-019-46731-6

  56. Ge P, Lei Z, Yu Y, Lu Z, Qiang L, Chai Q et al (2021) M . tuberculosis PknG manipulates host autophagy flux to promote pathogen intracellular survival. Autophagy 00:1–19. https://doi.org/10.1080/15548627.2021.1938912

    Article  CAS  Google Scholar 

  57. Khan MZ, Bhaskar A, Upadhyay S, Kumari P, Rajmani RS, Jain P et al (2017) Protein kinase G confers survival advantage to Mycobacterium tuberculosis during latency like conditions:1–28. https://doi.org/10.1074/jbc.M117.797563

  58. Khan MZ, Nandicoori VK (2021) Deletion of pknG abates reactivation of latent mycobacterium tuberculosis in mice. Antimicrob Agents Chemother 65(4):10–128. https://doi.org/10.1128/aac.02095-20

  59. Lima A, Leyva A, Rivera B, Magdalena M, Gil M (2021) Cascioferro A, et al, Proteome remodeling in the Mycobacterium tuberculosis PknG knockout : molecular evidence for the role of this kinase in cell envelope biogenesis and hypoxia response. 244. https://doi.org/10.1016/j.jprot.2021.104276

  60. Samuel LP, Song C, Wei J, Roberts EA, Dahl JL (2007) Barry CE, et al, Expression , production and release of the Eis protein by Mycobacterium tuberculosis during infection of macrophages and its effect on cytokine secretion Printed in Great Britain:529–540. https://doi.org/10.1099/mic.0.2006/002642-0

  61. Shin D, Jeon B, Lee H, Jin HS, Yuk J, Song C et al (2010) Mycobacterium tuberculosis Eis regulates autophagy , inflammation , and cell death through redox-dependent signaling. 6. https://doi.org/10.1371/journal.ppat.1001230

  62. Pan Q, Zhao F, Ye B (2018) Eis , a novel family of arylalkylamine. Sci Rep:1–8. https://doi.org/10.1038/s41598-018-20802-6

  63. Chen W, Green KD, Tsodikov O V, Garneau-tsodikova S. Aminoglycoside multiacetylating activity of the enhanced intracellular survival protein from Mycobacterium smegmatis and its inhibition. 2012;

    Book  Google Scholar 

  64. Zaunbrecher MA, Sikes Jr RD, Metchock B, Shinnick TM, Posey JE (2009) Overexpression of the chromosomally encoded aminoglycoside acetyltransferase eis confers kanamycin resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci 106(47):20004–20009. https://doi.org/10.1073/pnas.0907925106

  65. Chen W, Biswas T, Porter VR, Tsodikov OV, Garneau-tsodikova S (2011) Unusual regioversatility of acetyltransferase Eis , a cause of drug resistance in XDR-TB. 108:1–5. https://doi.org/10.1073/pnas.1105379108/-/DCSupplemental.www.pnas.org/cgi/doi/10.1073/pnas.1105379108

  66. Wong D, Bach H, Sun J, Hmama Z, Av-Gay Y (2011) Mycobacterium tuberculosis protein tyrosine phosphatase (PtpA) excludes host vacuolar-H +-ATPase to inhibit phagosome acidification. Proc Natl Acad Sci U S A 108:19371–19376. https://doi.org/10.1073/pnas.1109201108

    Article  PubMed  PubMed Central  Google Scholar 

  67. Cole S, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry Iii CE, Tekaia F (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 396(6707):190. https://doi.org/10.1038/24206

  68. Bach H, Papavinasasundaram KG, Wong D, Hmama Z, Av-Gay Y (2008) Mycobacterium tuberculosis virulence is mediated by PtpA dephosphorylation of human vacuolar protein sorting 33B. Cell Host Microbe 3:316–322. https://doi.org/10.1016/j.chom.2008.03.008

    Article  CAS  PubMed  Google Scholar 

  69. Wang J, Ge P, Qiang L, Tian F, Zhao D, Chai Q et al The mycobacterial phosphatase PtpA regulates the expression of host genes and promotes cell proliferation. Nat Commun. https://doi.org/10.1038/s41467-017-00279-z

  70. Brien JO, Hayder H, Zayed Y, Peng C (2018) Overview of microRNA biogenesis , mechanisms of actions , and circulation. 9:1–12. https://doi.org/10.3389/fendo.2018.00402

  71. Liu Y, Wang X, Jiang J, Cao Z, Yang B, Cheng X (2011) Modulation of T cell cytokine production by miR-144 * with elevated expression in patients with pulmonary tuberculosis. Mol Immunol 48:1084–1090. https://doi.org/10.1016/j.molimm.2011.02.001

    Article  CAS  PubMed  Google Scholar 

  72. Cui J, Li Z, Cui K, Gao Y, Zhang B, Niu J et al (2021) International immunopharmacology microRNA-20a-3p regulates the host immune response to facilitate the mycobacterium tuberculosis infection by targeting IKK β / NF- κ B pathway. Int Immunopharmacol 91:107286. https://doi.org/10.1016/j.intimp.2020.107286

    Article  CAS  PubMed  Google Scholar 

  73. Guo L, Zhao J, Qu Y, Yin R, Gao Q, Ding S (2016) MicroRNA-20a inhibits autophagic process by targeting ATG7 and ATG16L1 and favors mycobacterial survival in macrophage cells. 6:1–12. https://doi.org/10.3389/fcimb.2016.00134

  74. Ding S, Qu Y, Yang S, Xu G (2019) Novel miR-1958 promotes Mycobacterium tuberculosis survival in RAW264. 7 cells by inhibiting autophagy via Atg5. J Microbiol Biotechnol 29(6):989–998. https://doi.org/10.4014/jmb.1811.11062

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

    Article  CAS  PubMed  Google Scholar 

  76. Chen Z, Wang T, Liu Z, Zhang G, Wang J, Feng S et al (2015) Inhibition of autophagy by miR-30A induced by Mycobacteria tuberculosis as a possible mechanism of immune escape in human macrophages:420–424. https://doi.org/10.7883/yoken.JJID.2014.466

  77. Kumar R, Gupta P, Jana K, Gupta UD, Ghosh Z (2017) EBP β regulate innate immune signaling , the polarization of macrophages and the trafficking of Mycobacterium tuberculosis to lysosomes during infection. 1–29. https://doi.org/10.1371/journal.ppat.1006410

  78. Ouimet M, Koster S, Sakowski E, Ramkhelawon B, Van Solingen C, Oldebeken S et al (2016) Mycobacterium tuberculosis induces the miR-33 locus to reprogram autophagy and host lipid metabolism. Nat Immunol 17:677–686. https://doi.org/10.1038/ni.3434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Liu F, Chen J, Wang P, Li H, Zhou Y, Liu H et al Associated autophagy. Nat Commun. https://doi.org/10.1038/s41467-018-06836-4

  80. Strong EJ, Wang J, Ng TW, Porcelli SA, Lee S Mycobacterium tuberculosis PPE51 inhibits autophagy by suppressing Toll-like receptor 2-dependent signaling. MBio 13. https://doi.org/10.1128/mbio.02974-21

  81. Shariq M, Quadir N, Sharma N, Singh J, Sheikh JA, Khubaib M et al (2021) Mycobacterium tuberculosis RipA dampens TLR4-mediated host protective response using a multi-pronged approach involving autophagy , apoptosis , metabolic repurposing , and immune modulation. 12:1–19. https://doi.org/10.3389/fimmu.2021.636644

  82. Sinha S, Gupta G, Biswas S, Gupta K, Singh PP, Jain R et al (2022) Coronin-1 levels in patients with tuberculosis:866–870. https://doi.org/10.4103/ijmr.IJMR

  83. Mori M, Mode R, Pieters J (2018) From phagocytes to immune defense : roles for coronin proteins in Dictyostelium and mammalian immunity. 8:1–7. https://doi.org/10.3389/fcimb.2018.00077

  84. Jayachandran R, Sundaramurthy V, Combaluzier B, Mueller P, Korf H, Huygen K et al (2007) Survival of mycobacteria in macrophages is mediated by coronin 1-dependent activation of calcineurin:37–50. https://doi.org/10.1016/j.cell.2007.04.043

  85. Seto S, Tsujimura K, Koide Y (2012) Coronin-1a inhibits autophagosome formation around Mycobacterium tuberculosis -containing phagosomes and assists mycobacterial survival in macrophages. 14:710–727. https://doi.org/10.1111/j.1462-5822.2012.01754.x

  86. Turner J, Torrelles JB (2018) Mannose-capped lipoarabinomannan in Mycobacterium tuberculosis pathogenesis. https://doi.org/10.1093/femspd/fty026/4953419

  87. Correia-Neves M, Fröberg G, Korshun L, Viegas S, Vaz P, Ramanlal N et al Biomarkers for tuberculosis: the case for lipoarabinomannan. [cited 2022 1]; http://ow.ly/FyCs30n4uFEdoi. https://doi.org/10.1183/23120541.00115-2018

  88. De P, Amin AG, Flores D, Simpson A, Dobos K, Chatterjee D (2021) Structural implications of lipoarabinomannan glycans from global clinical isolates in diagnosis of Mycobacterium tuberculosis infection. J Biol Chem 297:101265. https://doi.org/10.1016/j.jbc.2021.101265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Welin A, Winberg ME, Abdalla H, Särndahl E, Rasmusson B, Stendahl O et al (2008) Incorporation of Mycobacterium tuberculosis lipoarabinomannan into macrophage membrane rafts is a prerequisite for the phagosomal maturation block. Infect Immun 76:2882–2887. https://doi.org/10.1128/IAI.01549-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Liu H, Gui X, Chen S, Fu W, Li X, Xiao T et al (2022) Structural variability of lipoarabinomannan modulates innate immune responses within infected alveolar epithelial cells. Cells:11. https://doi.org/10.3390/cells11030361

  91. Sibley LD, Hunter SW, Brennan PJ, Krahenbuhl JL (1988) Mycobacterial hpoarabinomannan inhibits gamma interferon-mediated activation of macrophages. Infect fmmun 56:1232–1236. https://doi.org/10.1128/iai.56.5.1232-1236.1988

  92. Chan J, Fan X, Hunter SW, Brennan PJ, Bloom BR (1991) Lipoarabinomannan, a possible virulence factor involved in persistence of Mycobacterium tuberculosis within macrophages. Infect Immun 59:1755–1761. https://doi.org/10.1128/iai.59.5.1755-1761.1991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Sengupta S, Nayak B, Meuli M, Sander P, Mishra S (2021) Mycobacterium tuberculosis phosphoribosyltransferase promotes bacterial survival in macrophages by inducing histone hypermethylation in autophagy-related genes. 11:1–13. https://doi.org/10.3389/fcimb.2021.676456

  94. Padhi A, Pattnaik K, Biswas M, Jagadeb M, Behera A, Alerts E (2019) Mycobacterium tuberculosis LprE suppresses TLR2-dependent cathelicidin and autophagy expression to enhance bacterial survival in macrophages. https://doi.org/10.4049/jimmunol.1801301

  95. Laopanupong T, Prombutara P, Kanjanasirirat P (2021) Lysosome repositioning as an autophagy escape mechanism by Mycobacterium tuberculosis Beijing strain. Sci Rep:1–17. https://doi.org/10.1038/s41598-021-83835-4

  96. Garg R, Borbora SM, Bansia H, Rao S, Singh P (2020) Mycobacterium tuberculosis calcium pump CtpF modulates the autophagosome in an mTOR-dependent manner. 10:1–13. https://doi.org/10.3389/fcimb.2020.00461

  97. Wallis RS, Hafner R (2015) Advancing host-directed therapy for tuberculosis. Nat Rev Immunol 15:255–263. https://doi.org/10.1038/nri3813

    Article  CAS  PubMed  Google Scholar 

  98. Kolloli A, Subbian S (2017) Host-directed therapeutic strategies for tuberculosis. Front Med:4. https://doi.org/10.3389/fmed.2017.00171

  99. Singhal A, Jie L, Kumar P, Hong GS, Leow MKS, Paleja B et al (2014) Metformin as adjunct antituberculosis therapy. Sci Transl Med:6. https://doi.org/10.1126/scitranslmed.3009885

  100. Krzysztof Ł, Liber S (2010) Metformin increases phagocytosis and acidifies lysosomal / endosomal compartments in AMPK-dependent manner in rat primary microglia:171–186. https://doi.org/10.1007/s00210-009-0477-x

  101. Padmapriydarsini C, Mamulwar M, Mohan A, Shanmugam P, Gomathy NS, Mane A et al (2022) Randomized trial of metformin with anti-tuberculosis drugs for early sputum conversion in adults with pulmonary tuberculosis. 75:425–434. https://doi.org/10.1093/cid/ciab964

  102. Ghidini M, Petrelli F, Ghidini A, Tomasello G, Hahne JC, Passalacqua R et al (2017) Clinical development of mTor inhibitors for renal cancer. Expert Opin Investig Drugs 26:1229–1237. https://doi.org/10.1080/13543784.2017.1384813

    Article  CAS  PubMed  Google Scholar 

  103. Neuhaus P, Klupp J, Langrehr JM (2001) mTOR inhibitors: an overview. Liver Transplant 7:473–484. https://doi.org/10.1053/jlts.2001.24645

    Article  CAS  Google Scholar 

  104. Gupta A, Pant G, Mitra K, Madan J, Chourasia MK, Misra A (2014) Inhalable particles containing rapamycin for induction of autophagy in macrophages infected with Mycobacterium tuberculosis. Mol Pharm 11:1201–1207. https://doi.org/10.1021/mp4006563

    Article  CAS  PubMed  Google Scholar 

  105. Gupta A, Sharma D, Meena J, Pandya S, Sachan M, Kumar S et al (2016) Preparation and preclinical evaluation of inhalable particles containing rapamycin and anti-tuberculosis agents for induction of autophagy. Pharm Res 33:1899–1912. https://doi.org/10.1007/s11095-016-1926-0

    Article  CAS  PubMed  Google Scholar 

  106. Bhatt K, Bhagavathula M, Verma S, Timmins GS, Deretic VP, Ellner JJ et al (2021) Rapamycin modulates pulmonary pathology in a murine model of Mycobacterium tuberculosis infection. DMM Dis Model Mech:14. https://doi.org/10.1242/dmm.049018

  107. Floto RA, Sarkar S, Perlstein EO, Kampmann B, Schreiber SL, Rubinsztein DC (2007) Erratum: Small molecule enhancers of rapamycin-induced TOR inhibition promote autophagy, reduce toxicity in Huntington’s disease models and enhance killing of mycobacteria by macrophages (Autophagy). Autophagy 3:620–622. https://doi.org/10.4161/auto.4898

    Article  CAS  PubMed  Google Scholar 

  108. Ashley D, Hernandez J, Cao R, To K, Yegiazaryan A, Abrahem R et al (2020) Antimycobacterial effects of everolimus in a human granuloma model. J Clin Med 9:1–14. https://doi.org/10.3390/jcm9072043

    Article  CAS  Google Scholar 

  109. Cao R, To K, Kachour N, Beever A, Owens J, Sathananthan A et al (2021) Everolimus-induced effector mechanism in macrophages and survivability of Erdman, CDC1551 and HN878 strains of Mycobacterium tuberculosis infection. Biomol Concepts 12:46–54. https://doi.org/10.1515/bmc-2021-0006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Wallis RS, Ginindza S, Beattie T, Arjun N, Sebe M, Likoti M et al (2021) Articles Adjunctive host-directed therapies for pulmonary tuberculosis : a prospective , open-label , phase 2 , randomised controlled trial. Lancet Respir 2600:1–12. https://doi.org/10.1016/S2213-2600(20)30448-3

    Article  Google Scholar 

  111. Sharma A, Vaghasiya K, Ray E, Gupta P, Gupta UD, Singh AK et al (2020) Targeted pulmonary delivery of the green tea polyphenol epigallocatechin gallate controls the growth of Mycobacterium tuberculosis by enhancing the autophagy and suppressing bacterial burden. ACS Biomater Sci Eng 6:4126–4140. https://doi.org/10.1021/acsbiomaterials.0c00823

    Article  CAS  PubMed  Google Scholar 

  112. Sultana Rekha R, Rao Muvva SJ, Wan M, Raqib R, Bergman P, Brighenti S et al (2015) Phenylbutyrate induces LL-37-dependent autophagy and intracellular killing of mycobacterium tuberculosis in human macrophages. Autophagy 11:1688–1699. https://doi.org/10.1080/15548627.2015.1075110

    Article  CAS  Google Scholar 

  113. Choi HH, Shin DM, Kang G, Kim KH, Park JB, Hur GM et al (2010) Endoplasmic reticulum stress response is involved in Mycobacterium tuberculosis protein ESAT-6-mediated apoptosis. FEBS Lett 584:2445–2454. https://doi.org/10.1016/j.febslet.2010.04.050

    Article  CAS  PubMed  Google Scholar 

  114. Cui Y, Zhao D, Barrow PA, Zhou X (2016) The endoplasmic reticulum stress response: a link with tuberculosis? Tuberculosis 97:52–56. https://doi.org/10.1016/j.tube.2015.12.009

    Article  CAS  PubMed  Google Scholar 

  115. Rekha RS, Mily A, Sultana T, Haq A, Ahmed S, Mostafa Kamal SM et al (2018) Immune responses in the treatment of drug-sensitive pulmonary tuberculosis with phenylbutyrate and vitamin D 3 as host directed therapy. BMC Infect. Dis. 18:1–12. https://doi.org/10.1186/s12879-018-3203-9

    Article  CAS  Google Scholar 

  116. Mily A, Rekha RS, Kamal SMM, Arifuzzaman ASM, Rahim Z, Khan L et al (2015) Significant effects of oral phenylbutyrate and vitamin D3 adjunctive therapy in pulmonary tuberculosis: a randomized controlled trial. PLoS One 10:1–25. https://doi.org/10.1371/journal.pone.0138340

    Article  CAS  Google Scholar 

  117. Keflie TS, Nölle N, Lambert C, Nohr D, Biesalski K (2015) Vitamin D Deficiencies among tuberculosis patients. Nutrition. https://doi.org/10.1016/j.nut.2015.05.003

  118. Talat N, Perry S, Parsonnet J (2010) Progression 16:853–855. https://doi.org/10.3201/eid1605.091693

    Article  CAS  Google Scholar 

  119. Hong JY, Kim SY, Chung KS, Kim EY, Jung JY, Park MS et al (2014) Association between vitamin D deficiency and tuberculosis in a Korean population. 18:73–78. https://doi.org/10.5588/ijtld.13.0536

  120. Jaimni V, Shasty BA, Madhyastha SP, Shetty GV, Acharya RV, Bekur R, Doddamani A (2021) Association of vitamin D deficiency and newly diagnosed pulmonary tuberculosis. Pulmonary medicine 2021:1–6. https://doi.org/10.1155/2021/5285841

  121. Wen Y, Li L, Deng Z (2022) Calcitriol supplementation accelerates the recovery of patients with tuberculosis who have vitamin D deficiency : a randomized , single - blind , controlled clinical trial. BMC Infect Dis:1–10. https://doi.org/10.1186/s12879-022-07427-x

  122. Grange JM, Snell NJC (1996) Activity of bromhexine and ambroxol, semi-synthetic derivatives of vasicine from the Indian shrub Adhatoda vasica, against Mycobacterium tuberculosis in vitro. J Ethnopharmacol 50:49–53. https://doi.org/10.1016/0378-8741(95)01331-8

    Article  CAS  PubMed  Google Scholar 

  123. Choi SW, Gu Y, Peters RS, Salgame P, Ellner JJ, Timmins GS et al (2018) Ambroxol induces autophagy and potentiates rifampin antimycobacterial activity. Antimicrob Agents Chemother:62. https://doi.org/10.1128/aac.01019-18

  124. Pickar JH, Komm BS (2015) Selective estrogen receptor modulators and the combination therapy conjugated estrogens/bazedoxifene: a review of effects on the breast. Post Reprod Heal 21:112–121. https://doi.org/10.1177/2053369115599090

    Article  Google Scholar 

  125. Ouyang Q, Zhang K, Lin D, Feng CG, Cai Y, Chen X (2020) Bazedoxifene suppresses intracellular Mycobacterium tuberculosis growth by enhancing autophagy. mSphere 5:1–10. https://doi.org/10.1128/msphere.00124-20

    Article  CAS  Google Scholar 

  126. Barrientos OM, Juárez E, Gonzalez Y, Castro-Villeda DA, Torres M, Guzmán-Beltrán S (2021) Loperamide exerts a direct bactericidal effect against M. tuberculosis, M. bovis, M. terrae and M. smegmatis. Lett. Appl. Microbiol 72:351–356. https://doi.org/10.1111/lam.13432

    Article  CAS  Google Scholar 

  127. Juárez E, Ruiz A, Cortez O, Sada E, Torres M (2018) Antimicrobial and immunomodulatory activity induced by loperamide in mycobacterial infections. Int Immunopharmacol 65:29–36. https://doi.org/10.1016/j.intimp.2018.09.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Martineau AR, Wilkinson KA, Newton SM, Floto RA, Norman AW, Skolimowska K et al (2007) IFN-γ- and TNF-independent vitamin D-inducible human suppression of mycobacteria: the role of cathelicidin LL-37. J Immunol 178:7190–7198. https://doi.org/10.4049/jimmunol.178.11.7190

    Article  CAS  PubMed  Google Scholar 

  129. Bruiners N, Dutta NK, Guerrini V, Salamon H, Yamaguchi KD, Karakousis PC et al (2020) The anti-tubercular activity of simvastatin is mediated by cholesterol-driven autophagy via the AMPK-mTORC1-TFEB axis. J Lipid Res 61:1617–1628. https://doi.org/10.1194/jlr.RA120000895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Sleat DE, Wiseman JA, El-Banna M, Price SM, Verot L, Shen MM et al (2004) Genetic evidence for nonredundant functional cooperativity between NPC1 and NPC2 in lipid transport. Proc Natl Acad Sci U S A 101:5886–5891. https://doi.org/10.1073/pnas.0308456101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Xu J, Dang Y, Ren YR, Liu JO (2010) Cholesterol trafficking is required for mTOR activation in endothelial cells. Proc Natl Acad Sci U S A 107:4764–4769. https://doi.org/10.1073/pnas.0910872107

    Article  PubMed  PubMed Central  Google Scholar 

  132. Guerra-De-Blas PDC, Bobadilla-Del-Valle M, Sada-Ovalle I, Estrada-García I, Torres-González P, López-Saavedra A et al (2019) Simvastatin enhances the immune response against Mycobacterium tuberculosis. Front Microbiol 10:1–14. https://doi.org/10.3389/fmicb.2019.02097

    Article  Google Scholar 

  133. Cross GB, Sari IP, Kityo C, Lu Q, Pokharkar Y, Moorakonda RB et al (2023) Rosuvastatin adjunctive therapy for rifampicin-susceptible pulmonary tuberculosis: a phase 2b, randomised, open-label, multicentre trial. Lancet Infect Dis 23(23):847–855 https://doi.org/http://www.ncbi.nlm.nih.gov/pubmed/36966799

    Article  CAS  PubMed  Google Scholar 

  134. Lee HJ, Ko HJ, Kim SH, Jung YJ (2019) Pasakbumin A controls the growth of Mycobacterium tuberculosis by enhancing the autophagy and production of antibacterial mediators in mouse macrophages. PLoS One 14:1–19. https://doi.org/10.1371/journal.pone.0199799

    Article  CAS  Google Scholar 

  135. Tong Y, Song F (2015) Intracellular calcium signaling regulates autophagy via calcineurin-mediated TFEB dephosphorylation. Autophagy 11:1192–1195. https://doi.org/10.1080/15548627.2015.1054594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Mawatwal S, Behura A, Ghosh A, Kidwai S, Mishra A, Deep A et al (2017) Calcimycin mediates mycobacterial killing by inducing intracellular calcium-regulated autophagy in a P2RX7 dependent manner. Biochim Biophys Acta - Gen Subj 1861:3190–3200. https://doi.org/10.1016/j.bbagen.2017.09.010

    Article  CAS  PubMed  Google Scholar 

  137. Blay JY, Von Mehren M (2011) Nilotinib: a novel, selective tyrosine kinase inhibitor. Semin Oncol 38:S3–S9. https://doi.org/10.1053/j.seminoncol.2011.01.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Mahadik K, Prakhar P, Rajmani RS, Singh A, Balaji KN (2018) c-Abl-TWIST1 epigenetically dysregulate inflammatory responses during mycobacterial infection by co-regulating bone morphogenesis protein and miR27a. Front Immunol 9:1–19. https://doi.org/10.3389/fimmu.2018.00085

    Article  CAS  Google Scholar 

  139. Hussain T, Zhao D, Shah SZA, Sabir N, Wang J, Liao Y et al (2019) Nilotinib: a tyrosine kinase inhibitor mediates resistance to intracellular mycobacterium via regulating autophagy. Cells:8. https://doi.org/10.3390/cells8050506

  140. Wang J, Sha J, Strong E, Chopra AK, Lee S (2022) FDA-approved amoxapine effectively promotes macrophage control of mycobacteria by inducing autophagy. Microbiology Spectrum 10(5):e02509–22. https://doi.org/10.1128/spectrum.02509-22

  141. Fassnacht M, Berruti A, Baudin E, Demeure MJ, Gilbert J, Haak H et al (2015) Linsitinib ( OSI-906 ) versus placebo for patients with locally advanced or metastatic adrenocortical carcinoma : a double-blind , randomised , phase 3 study. Lancet Oncol 16:426–435. https://doi.org/10.1016/S1470-2045(15)70081-1

    Article  CAS  PubMed  Google Scholar 

  142. Bendell JC, Jones SF, Hart L, Spigel DR, Lane CM, Earwood C et al (2015) A phase Ib study of linsitinib ( OSI-906 ), a dual inhibitor of IGF-1R and IR tyrosine kinase , in combination with everolimus as treatment for patients with refractory metastatic colorectal cancer:187–193. https://doi.org/10.1007/s10637-014-0177-3

  143. Barata P, Cooney M, Tyler A, Wright J, Dreicer R, Garcia JA (2018) A phase 2 study of OSI-906 (linsitinib, an insulin-like growth factor receptor-1 inhibitor) in patients with asymptomatic or mildly symptomatic (non-opioid requiring) metastatic castrate resistant prostate cancer (CRPC). Investigational New Drugs 36:451–457. https://doi.org/10.1007/s10637-018-0574-0

  144. Wang H, Bi J, Zhang Y, Pan M, Guo Q, Xiao G et al (2022) Human kinase IGF1R/IR inhibitor linsitinib controls the in vitro and intracellular growth of. https://doi.org/10.1021/acsinfecdis.2c00278

  145. Xu S, Liu X, Zhan P (2022) SMIP-30, a potent and selective PPM1A inhibitor with potential to treat tuberculosis. Acta Pharm Sin B 12:4519–4521. https://doi.org/10.1016/J.APSB.2022.10.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Caron A, Richard D, Laplante M The roles of mTOR complexes in lipid metabolism:321–350. https://doi.org/10.1146/annurev-nutr-071714-034355

  147. Houde VP, Bru S, Festuccia WT, Blanchard P, Bellmann K (2010) Deshaies Y, Chronic rapamycin treatment causes glucose intolerance and hyperlipidemia by upregulating hepatic gluconeogenesis and impairing lipid deposition in adipose tissue. 59. https://doi.org/10.2337/db09-1324.V.P.H

  148. Liu X, Zhang Y, Ni M, Cao H, Signer RAJ, Li D et al (2017) Regulation of mitochondrial biogenesis in erythropoiesis by mTORC1-mediated protein translation. 19. https://doi.org/10.1038/ncb3527

  149. Knight ZA, Schmidt SF, Birsoy K, Tan K, Friedman JM (2014) A critical role for mTORC1 in erythropoiesis and anemia:1–17. https://doi.org/10.7554/eLife.01913

  150. Martins F, Augusto M, Oliveira D, Wang Q, Sonis S, Gallottini M et al (2013) A review of oral toxicity associated with mTOR inhibitor therapy in cancer patients. Oral Oncol 49:293–298. https://doi.org/10.1016/j.oraloncology.2012.11.008

    Article  CAS  PubMed  Google Scholar 

  151. Rugo HS, Hortobagyi GN, Yao J, Pavel M, Ravaud A, Franz D et al (2016) Meta-analysis of stomatitis in clinical studies of everolimus : incidence and relationship with efficacy. https://doi.org/10.1093/annonc/mdv595

  152. Gallagher EJ, Fierz Y, Vijayakumar A, Haddad N, Yakar S, Leroith D (2011) Inhibiting PI3K reduces mammary tumor growth and induces hyperglycemia in a mouse model of insulin resistance and hyperinsulinemia. 31:3213–3222. https://doi.org/10.1038/onc.2011.495

  153. Galanis E, Buckner JC, Maurer MJ, Kreisberg JI, Ballman K, Boni J et al (2015) Phase II trial of temsirolimus ( CCI-779 ) in recurrent glioblastoma multiforme : a North Central Cancer Treatment Group Study. 23. https://doi.org/10.1200/JCO.2005.23.622

  154. First B, Paper E (2014) Title:617–632. https://doi.org/10.1182/blood-2013-11-535047

  155. Lampson BL, Kasar SN, Matos TR, Morgan EA, Rassenti L, Davids MS et al (2016) Idelalisib given front-line for treatment of chronic lymphocytic leukemia causes frequent immune-mediated hepatotoxicity. 128:195–204. https://doi.org/10.1182/blood-2016-03-707133

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Acknowledgements

We are thankful to the Department of Biotechnology, Ministry of Science and Technology, New Delhi, India, for supporting tuberculosis research by awarding Ramalingaswami Fellowship to NPK (D.O.NO.BT/HRD/35/02/2006; No. BT/RLF/Re-entry 66/2017; GAP-39).

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  1. Department of Biological Sciences (Pharmacology and Toxicology), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, 500037, India

    Pavan Kumar Nagdev, Puja Kumari Agnivesh, Arnab Roy, Shashikanta Sau & Nitin Pal Kalia

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PKN and NPK conceptualized the idea of the review and literature search and drafted the review. PKA supported PKN in drafting the manuscript. AR and SS analyzed and edited the review. PKN, PKA, and NPK finalized and validated the review article. All authors have read and approved the final version of the manuscript.

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Nagdev, P.K., Agnivesh, P.K., Roy, A. et al. Exploring and exploiting the host cell autophagy during Mycobacterium tuberculosis infection. Eur J Clin Microbiol Infect Dis 42, 1297–1315 (2023). https://doi.org/10.1007/s10096-023-04663-0

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