ESAT-6
{{Short description|Protein made by Mycobacterium tuberculosis}}
{{infobox protein
| Name = 6 kDa early secretory antigenic target
| image =
| width =
| caption =
| Symbol = esxA
| AltSymbols =
| ATC_prefix=
| ATC_suffix=
| ATC_supplemental=
| CAS_number=
| CAS_supplemental=
| DrugBank=
| EntrezGene = 886209
| HGNCid =
| OMIM =
| PDB = 3FAV
| RefSeq =
| UniProt = P0A564
| ECnumber =
| Chromosome =
| Arm =
| Band =
| LocusSupplementaryData =
}}
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 }}
ESAT-6 and CFP-10
File:MTBVAC cell compared to Mycobacterium tuberculosis.png
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.{{Cite journal |last1=Renshaw |first1=Philip S |last2=Lightbody |first2=Kirsty L |last3=Veverka |first3=Vaclav |last4=Muskett |first4=Fred W |last5=Kelly |first5=Geoff |last6=Frenkiel |first6=Thomas A |last7=Gordon |first7=Stephen V |last8=Hewinson |first8=R Glyn |last9=Burke |first9=Bernard |last10=Norman |first10=Jim |last11=Williamson |first11=Richard A |date=2005-07-20 |title=Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6 |journal=The EMBO Journal |volume=24 |issue=14 |pages=2491–2498 |doi=10.1038/sj.emboj.7600732 |issn=0261-4189 |pmc=1176459 |pmid=15973432}} Recent work shows that the production of these proteins is a process that is caused by the flanking genes.{{Cite web |title=DNA Flanking Region - an overview {{!}} ScienceDirect Topics |url=https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/dna-flanking-region |access-date=2022-05-05 |website=www.sciencedirect.com}} 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.{{Cite web |title=Early Secretory Antigenic Target 6 - an overview {{!}} ScienceDirect Topics |url=https://www.sciencedirect.com/topics/medicine-and-dentistry/early-secretory-antigenic-target-6 |access-date=2022-05-05 |website=www.sciencedirect.com}}