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. 2021 Oct 3;20:129. doi: 10.1186/s12944-021-01550-5

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 2 — Survival strategies of M. tuberculosis inside the phagosome environment. This figure illustrates the mechanisms proposed to allow Mtb to survive inside the phagosome or Mtb escaping mechanisms from host defense. (1) Mtb survives inside the hostile phagosome by expressing Mycobacterial acid resistance Protein (MarP), a protein that buffers the acidic milieu. (2) Mtb survives inside the phagosome and evades the host immune response by residing apposition to the host lipid droplet. (3) Mtb avoids phagosome maturation and phagolysosome fusion by tagging early endosome markers (Rab5, Rab11, coronin1/TACO) and avoiding attachment and activation of several others (Rab7, CD63, lysosomal hydrolase, cathepsin D), which inhibits the proton–ATPase activity. Mtb accomplishes this by expressing various virulent factor lipoproteins (Man LAM, secreted phosphatase, lipid phosphatidylinositol 3 phosphate, phosphatase ptpA, TDM). (4) Mtb exits the phagosome and replicates inside the cytoplasm by rupturing the phagosome expressing ESX-1, DIM/PDIM, and phospho lipase A2 [46]. This phagosomal escape is advantageous to the pathogen for acquiring essential amino acids (arginine, methionine, or leucine), replication and dissemination [47]. Mtb: M. tuberculosis; Man LAM: Mannosylated lipoarabinomannan; TDM: Trehalose-6,6′-dimycolate; ESX-1: Early secretary antigenic target 6 (ESAT6) secretion system like protein; TACO: tryptophan aspartate containing coat protein, also named P57, Coronin1; DIM/PDIM: phthiocerol dimycocerosates. Figure is created with BioRender.com