ESAT-6

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6 kDa early secretory antigenic target
Identifiers
SymbolesxA
NCBI gene886209
PDB3FAV
UniProtP0A564
Search for
StructuresSwiss-model
DomainsInterPro

ESAT-6 or early secreted antigenic target 6 kDa, is produced by Mycobacterium tuberculosis, it is a secretory protein and potent T cell antigen.[1] It is used in tuberculosis diagnosis by the whole blood interferon γ test QuantiFERON-TB Gold, in conjunction with CFP-10.

ESAT-6 has been shown to directly bind to the TLR2 receptor, inhibiting downstream signal transduction.[2] It has also been studied that the inactivation of ESAT-6 leads to decreased virulence of M. tuberculosis.[3] Secretion of the ESAT-6 protein is one of the main determining factors in the virulence of the M. tuberculosis.[3] ESAT-6 has more commonly become a marker for the TB diagnosis and treatment.[4] There is also the use of the ESAT increase the production of virulent factors that cause for the increase in pathogenicity of TB.[5]

ESAT-6 is one of the main proteins that is inhibited in the production of vaccines for M. tuberculosis[3][6] with the combination of the increased antigenic factors agβ5-A and the agβ5-C.[6] There are studies that are currently trying to connect the linkage between ESAT-6 and the epithelial cells that are in the lungs, which has shown the dependence on the induction of the IL-8 promoter.[7]

ESAT-6 and CFP-10

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The phoP and fadD26 rational inactivation in MTBVAC results in virulence attenuation and enhanced immunogenicity relative to the M. tuberculosis pathogen

There are also connections between the ESAT-6 marker and the CFP-10 marker. These are both being produced in Mycobacterium tuberculosis cells and is subject to the positive correlation of virulence to the amount of protein produced.[8] Recent work shows that the production of these proteins is a process that is caused by the flanking genes.[8][9] ESAT-6 and CFP-10 have also been increasingly used for in house antigen tests that now allow for quick testing of antibodies for the use of TB, but there are still determinations being made on what levels of these antigens or antibiodies would be considered normal.[10]

Microscope view of M. tuberculosis

See also

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References

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  1. ^ "Entrez gene".
  2. ^ Pathak SK, Basu S, Basu KK, Banerjee A, Pathak S, Bhattacharyya A, Kaisho T, Kundu M, Basu J (June 2007). "Direct extracellular interaction between the early secreted antigen ESAT-6 of Mycobacterium tuberculosis and TLR2 inhibits TLR signaling in macrophages". Nat. Immunol. 8 (6): 610–8. doi:10.1038/ni1468. PMID 17486091. S2CID 22486299.
  3. ^ a b c Sreejit, Gopalkrishna; Ahmed, Asma; Parveen, Nazia; Jha, Vishwanath; Valluri, Vijaya Lakshmi; Ghosh, Sudip; Mukhopadhyay, Sangita (2014-10-30). "The ESAT-6 Protein of Mycobacterium tuberculosis Interacts with Beta-2-Microglobulin (β2M) Affecting Antigen Presentation Function of Macrophage". PLOS Pathogens. 10 (10): e1004446. doi:10.1371/journal.ppat.1004446. ISSN 1553-7374. PMC 4214792. PMID 25356553.
  4. ^ Gey van Pittius, Nico C.; Warren, Robin M.; van Helden, Paul D. (November 2002). "ESAT-6 and CFP-10: What Is the Diagnosis?". Infection and Immunity. 70 (11): 6509–6511. doi:10.1128/IAI.70.11.6509-6511.2002. ISSN 0019-9567. PMC 130415. PMID 12379740.
  5. ^ Yang, Shaojun; Li, Fake; Jia, Shuangrong; Zhang, Kejun; Jiang, Wenbing; Shang, Ya; Chang, Kai; Deng, Shaoli; Chen, Ming (2015). "Early Secreted Antigen ESAT-6 of Mycobacterium Tuberculosis Promotes Apoptosis of Macrophages via Targeting the MicroRNA155-SOCS1 Interaction". Cellular Physiology and Biochemistry. 35 (4): 1276–1288. doi:10.1159/000373950. ISSN 1015-8987. PMID 25721573. S2CID 4933280.
  6. ^ a b Dietrich, Jes; Andersen, Claire; Rappuoli, Rino; Doherty, T. Mark; Jensen, Charlotte Green; Andersen, Peter (2006-11-01). "Mucosal Administration of Ag85B-ESAT-6 Protects against Infection with Mycobacterium tuberculosis and Boosts Prior Bacillus Calmette-Guérin Immunity". The Journal of Immunology. 177 (9): 6353–6360. doi:10.4049/jimmunol.177.9.6353. ISSN 0022-1767. PMID 17056566. S2CID 17983383.
  7. ^ Boggaram, Vijay; Gottipati, Koteswara R.; Wang, Xisheng; Samten, Buka (2013-08-30). "Early secreted antigenic target of 6 kDa (ESAT-6) protein of Mycobacterium tuberculosis induces interleukin-8 (IL-8) expression in lung epithelial cells via protein kinase signaling and reactive oxygen species". The Journal of Biological Chemistry. 288 (35): 25500–25511. doi:10.1074/jbc.M112.448217. ISSN 1083-351X. PMC 3757211. PMID 23867456.
  8. ^ a b Renshaw, Philip S; Lightbody, Kirsty L; Veverka, Vaclav; Muskett, Fred W; Kelly, Geoff; Frenkiel, Thomas A; Gordon, Stephen V; Hewinson, R Glyn; Burke, Bernard; Norman, Jim; Williamson, Richard A (2005-07-20). "Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6". The EMBO Journal. 24 (14): 2491–2498. doi:10.1038/sj.emboj.7600732. ISSN 0261-4189. PMC 1176459. PMID 15973432.
  9. ^ "DNA Flanking Region - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2022-05-05.
  10. ^ "Early Secretory Antigenic Target 6 - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2022-05-05.
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