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      ESX secretion system: The gatekeepers of mycobacterial survivability and pathogenesis

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          Abstract

          Mycobacterium tuberculosis, the causative agent of Tuberculosis has plagued humankind for ages and has surfaced stronger than ever with the advent of drug resistance. Mycobacteria are adept at evading the host immune system and establishing infection by engaging host factors and secreting several virulence factors. Hence these secretion systems play a key role in mycobacterial pathogenesis. The type VII secretion system or ESX (early secretory antigenic target (ESAT6) secretion) system is one such crucial system that comprises five different pathways having distinct roles in mycobacterial proliferation, pathogenesis, cytosolic escape within macrophages, regulation of macrophage apoptosis, metal ion homeostasis, etc. ESX 1–5 systems are implicated in the secretion of a plethora of proteins, of which only a few are functionally characterized. Here we summarize the current knowledge of ESX secretion systems of mycobacteria with a special focus on ESX-1 and ESX-5 systems that subvert macrophage defenses and help mycobacteria to establish their niche within the macrophage.

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          Most cited references74

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          The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins.

          Selective trafficking of membrane proteins to lysosomes for destruction is required for proper cell signalling and metabolism. Ubiquitylation aids this process by specifying which proteins should be transported to the lysosome lumen by the multivesicular endosome pathway. The endosomal sorting complex required for transport (ESCRT) machinery sorts cargo labelled with ubiquitin into invaginations of endosome membranes. Then, through a highly conserved mechanism also used in cytokinesis and viral budding, it mediates the breaking off of the cargo-containing intraluminal vesicles from the perimeter membrane. The involvement of the ESCRT machinery in suppressing diseases such as cancer, neurodegeneration and infections underscores its importance to the cell.
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            Molecular Basis of Bacterial Outer Membrane Permeability Revisited

            H Nikaido (2003)
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              • Article: not found

              Type VII secretion--mycobacteria show the way.

              Recent evidence shows that mycobacteria have developed novel and specialized secretion systems for the transport of extracellular proteins across their hydrophobic, and highly impermeable, cell wall. Strikingly, mycobacterial genomes encode up to five of these transport systems. Two of these systems, ESX-1 and ESX-5, are involved in virulence - they both affect the cell-to-cell migration of pathogenic mycobacteria. Here, we discuss this novel secretion pathway and consider variants that are present in various Gram-positive bacteria. Given the unique composition of this secretion system, and its general importance, we propose that, in line with the accepted nomenclature, it should be called type VII secretion.
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                Author and article information

                Contributors
                Journal
                1886
                European Journal of Microbiology and Immunology
                Akadémiai Kiadó (Budapest )
                2062-8633
                11 December 2020
                10 November 2020
                : 10
                : 4
                : 202-209
                Affiliations
                [1] Department of Biotechnology, Molecular Immunology and Cellular Microbiology Laboratory, Indian Institute of Technology Kharagpur , Kharagpur 721302, India
                Author notes
                [* ]Corresponding author. somdeb@ 123456iitkgp.ac.in
                Author information
                https://orcid.org/0000-0001-5446-9582
                Article
                10.1556/1886.2020.00028
                caaa1e0c-cd78-4445-8625-4014b1fd6046
                © 2020 The Author(s)

                Open Access. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited, a link to the CC License is provided, and changes – if any – are indicated.

                History
                : 27 August 2020
                : 25 September 2020
                Page count
                Figures: 4, Equations: 0, References: 75, Pages: 08
                Funding
                Funded by: DST
                Award ID: YSS/2015/000471
                Funded by: DBT
                Award ID: BT/RLF/Re-entry/33/2014
                Categories
                Review Paper

                Medicine,Immunology,Public health,Microbiology & Virology,Infectious disease & Microbiology
                cell death,mycobacterium,ESX secretion system,phagosomal rupture

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