ESAT-6

{{Short description|Protein made by Mycobacterium tuberculosis}}

{{infobox protein

| Name = 6 kDa early secretory antigenic target

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| Symbol = esxA

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| EntrezGene = 886209

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| PDB = 3FAV

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| UniProt = P0A564

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ESAT-6 or early secreted antigenic target 6 kDa, is produced by Mycobacterium tuberculosis, it is a secretory protein and potent T cell antigen.{{cite web|url=https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=886209&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum|title=Entrez gene}} 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.{{cite journal|pmid=17486091|title=Direct extracellular interaction between the early secreted antigen ESAT-6 of Mycobacterium tuberculosis and TLR2 inhibits TLR signaling in macrophages.

|vauthors=Pathak SK, Basu S, Basu KK, Banerjee A, Pathak S, Bhattacharyya A, Kaisho T, Kundu M, Basu J | doi=10.1038/ni1468 | volume=8|issue=6|date=June 2007|journal=Nat. Immunol.|pages=610–8|s2cid=22486299

}} It has also been studied that the inactivation of ESAT-6 leads to decreased virulence of M. tuberculosis.{{Cite journal |last1=Sreejit |first1=Gopalkrishna |last2=Ahmed |first2=Asma |last3=Parveen |first3=Nazia |last4=Jha |first4=Vishwanath |last5=Valluri |first5=Vijaya Lakshmi |last6=Ghosh |first6=Sudip |last7=Mukhopadhyay |first7=Sangita |date=2014-10-30 |title=The ESAT-6 Protein of Mycobacterium tuberculosis Interacts with Beta-2-Microglobulin (β2M) Affecting Antigen Presentation Function of Macrophage |journal=PLOS Pathogens |language=en |volume=10 |issue=10 |pages=e1004446 |doi=10.1371/journal.ppat.1004446 |issn=1553-7374 |pmc=4214792 |pmid=25356553 |doi-access=free }} Secretion of the ESAT-6 protein is one of the main determining factors in the virulence of the M. tuberculosis. ESAT-6 has more commonly become a marker for the TB diagnosis and treatment.{{Cite journal |last1=Gey van Pittius |first1=Nico C. |last2=Warren |first2=Robin M. |last3=van Helden |first3=Paul D. |date=November 2002 |title=ESAT-6 and CFP-10: What Is the Diagnosis? |journal=Infection and Immunity |volume=70 |issue=11 |pages=6509–6511 |doi=10.1128/IAI.70.11.6509-6511.2002 |issn=0019-9567 |pmid=12379740|pmc=130415 }} There is also the use of the ESAT increase the production of virulent factors that cause for the increase in pathogenicity of TB.{{Cite journal |last1=Yang |first1=Shaojun |last2=Li |first2=Fake |last3=Jia |first3=Shuangrong |last4=Zhang |first4=Kejun |last5=Jiang |first5=Wenbing |last6=Shang |first6=Ya |last7=Chang |first7=Kai |last8=Deng |first8=Shaoli |last9=Chen |first9=Ming |date=2015 |title=Early Secreted Antigen ESAT-6 of Mycobacterium Tuberculosis Promotes Apoptosis of Macrophages via Targeting the MicroRNA155-SOCS1 Interaction |url=https://www.karger.com/Article/FullText/373950 |journal=Cellular Physiology and Biochemistry |language=english |volume=35 |issue=4 |pages=1276–1288 |doi=10.1159/000373950 |issn=1015-8987 |pmid=25721573|s2cid=4933280 |doi-access=free }}

ESAT-6 is one of the main proteins that is inhibited in the production of vaccines for M. tuberculosis{{Cite journal |last1=Dietrich |first1=Jes |last2=Andersen |first2=Claire |last3=Rappuoli |first3=Rino |last4=Doherty |first4=T. Mark |last5=Jensen |first5=Charlotte Green |last6=Andersen |first6=Peter |date=2006-11-01 |title=Mucosal Administration of Ag85B-ESAT-6 Protects against Infection with Mycobacterium tuberculosis and Boosts Prior Bacillus Calmette-Guérin Immunity |url=https://www.jimmunol.org/content/177/9/6353 |journal=The Journal of Immunology |language=en |volume=177 |issue=9 |pages=6353–6360 |doi=10.4049/jimmunol.177.9.6353 |issn=0022-1767 |pmid=17056566|s2cid=17983383 |doi-access=free }} with the combination of the increased antigenic factors agβ5-A and the agβ5-C. 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.{{Cite journal |last1=Boggaram |first1=Vijay |last2=Gottipati |first2=Koteswara R. |last3=Wang |first3=Xisheng |last4=Samten |first4=Buka |date=2013-08-30 |title=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 |journal=The Journal of Biological Chemistry |volume=288 |issue=35 |pages=25500–25511 |doi=10.1074/jbc.M112.448217 |issn=1083-351X |pmc=3757211 |pmid=23867456|doi-access=free }}