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Early Secretory Antigenic Target-6 (ESAT-6), also known as EsxA, is a potent virulence factor and highly immunodominant antigen secreted by Mycobacterium tuberculosis via the ESX-1 type VII secretion system. It typically forms a 1:1 heterodimer with its partner protein, Culture Filtrate Protein 10 (CFP-10), which is essential for its stability and secretion. ESAT-6 plays a critical role in pathogenesis by disrupting host cell membranes, facilitating the escape of the bacteria from the phagosome into the cytosol, and modulating the host immune response to favor bacterial persistence. Due to its absence in the Mycobacterium bovis BCG vaccine strain, ESAT-6 is a primary component in modern diagnostic Interferon-Gamma Release Assays (IGRAs) used to distinguish between tuberculosis infection and BCG vaccination. Furthermore, it is a major target in the development of next-generation subunit vaccines and potential anti-virulence therapies aimed at neutralizing its membrane-lytic activity.
ESAT-6 serves primarily as a potent T-cell antigen used in subunit vaccines to elicit a protective immune response and as a specific diagnostic marker to identify Mycobacterium tuberculosis infection by stimulating interferon-gamma production from sensitized T-cells.
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