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. 2021 Jan 14;11:614313. doi: 10.3389/fmicb.2020.614313

TABLE 1.

Summary of current experimental treatments inducing autophagy during M. tuberculosis infection.

Drug Model Mode References
Small Molecule Enhancers of Rapamycin M. bovis BCG infection of primary human macrophages Induce autophagy independently of mTOR Floto et al., 2007
Rifampicin Mtb infection of human differentiated monocytes Increased autolysosome formation, directly antimycobacterial Genestet et al., 2018
Linezolid Mtb infection of human differentiated monocytes Increased autophagosomes production, directly antimycobacterial Genestet et al., 2018
Bedaquiline Mtb infection of human differentiated monocytes Increased autophagosomes production, directly antimycobacterial Genestet et al., 2018
Nitazoxanide Mtb infection of human differentiated monocytes. M. leprae infection of mice Increased autophagy by inhibition of NADPH quinone oxidoreductase 1 leading to mTOR inhibition by TSC2 Lam et al., 2012; Bailey et al., 2017
Baicalin Mtb infection of mouse macrophages Induce autophagy via the PI3K/Akt/mTOR pathway, inhibit NLRP3 inflammasome activation via the PI3K/Akt/NF-κB, reduction of proinflammatory cytokines Lin et al., 2013; Zhang et al., 2017
Vitamin D Mtb/HIV co-infection model of primary human macrophages Cathelicidin dependent induction of autophagy Liu et al., 2007; Martineau et al., 2007; Yuk et al., 2009; Jo, 2010; Campbell and Spector, 2012b
4-phenylbutyrate Mtb infection of human monocytes Induction of LL-37 promoting autophagy via P2RX7 receptor, increasing free Ca2+ and activation of AMPK and PtdIns3K pathway. Rekha et al., 2015
Gefitinib Mtb infection of murine bone marrow-derived macrophages STAT3 dependent cytokine responses, increasing lysosomal trafficking Stanley et al., 2014; Sogi et al., 2017
Carbamazepine Mtb infection of human-derived macrophages or murine alveolar macrophages. M. marinum zebrafish model of infection. MDR Mtb infection of C57BL/6 mice Induce autophagy by blocking myoinositol uptake, decreasing phosphatidylinositol, and activating AMP kinase in an mTOR independent manner. Schiebler et al., 2015; Juárez et al., 2016
Valproic acid Mtb infection of human-derived macrophages or murine alveolar macrophages Increases colocalization of LC3 with Mtb Schiebler et al., 2015; Juárez et al., 2016
Loperamide Mtb infection of human-derived macrophages or murine alveolar macrophages Increases colocalization of LC3 with Mtb and reduces TNF-α production Juárez et al., 2016
Simvastatin Mtb infection of C57BL/6 mice Reduction of membrane cholesterol levels promotes phagosomal maturation and autophagy Parihar et al., 2013
Metformin Mtb infection of C57BL/6 mice Induction of mitochondrial reactive oxygen species, AMPK activation, and autophagy induction Singhal et al., 2014; Restrepo, 2016
Trehalose Mtb/M. avium/M. fortuitum infection of human differentiated monocytes Increase autophagy flux through activation of ptdIns3P by activation of PIKFYVE Sarkar et al., 2007; Sharma et al., 2020
Mycobacterial PILAM Mtb infection of murine macrophages Induction of autophagy and pro-inflammatory cytokines, enhanced colocalization of Mtb with phagolysosomes Shui et al., 2011; Singh et al., 2019
Nordi-hydroguaiaretic acid Avirulent Mtb infection of human differentiated monocytes Directly antimycobacterial, induce autophagosome formation and colocalization with Mtb Guzmán-Beltrán et al., 2016
Lactoferricin peptides M. avium infection of murine bone marrow macrophages Increased autophagosome formation Silva et al., 2017b