6-kDa early secreted antigenic target (ESAT-6) (ESAT-6)

The 6-kDa early secreted antigenic target (ESAT-6), also known as EsxA, is a critical virulence factor produced by Mycobacterium tuberculosis and secreted via the ESX-1 type VII secretion system (UniProt P9WNK5). It typically functions as a 1:1 heterodimer with its partner protein, Culture Filtrate Protein 10 (CFP-10), which is essential for its stability and secretion (PubMed: 10966465). ESAT-6 is instrumental in tuberculosis pathogenesis, as it facilitates the translocation of the bacteria from the host phagosome into the cytosol by disrupting the phagosomal membrane (PubMed: 17556505). Because ESAT-6 is present in virulent M. tuberculosis but absent in the Mycobacterium bovis BCG vaccine strain, it is a cornerstone of modern tuberculosis diagnostics, specifically Interferon-Gamma Release Assays (IGRAs) (PubMed: 15139871). It is also a primary candidate for inclusion in next-generation subunit vaccines designed to boost T-cell immunity (PubMed: 21402767). Additionally, the ESAT-6/CFP-10 complex is a target for novel anti-virulence drug discovery efforts aimed at inhibiting bacterial dissemination without exerting the selective pressure associated with traditional antibiotics (PubMed: 29339411).

Other names

EsxAEarly secreted antigenic target 6Early secretory antigenic target-6ESAT6Rv3875

ESAT-6 acts as a potent T-cell antigen in vaccines to elicit Th1-mediated immune responses; in diagnostics, it serves as a specific stimulant for interferon-gamma release from sensitized T-cells; as a therapeutic target, experimental inhibitors aim to block its secretion or its interaction with CFP-10 to prevent phagosomal escape.