ESX1

ESX-1, also known as the ESX-1 secretion system or type VII secretion system 1 (T7SS-1), is a specialized protein export system found in the Mycobacterium tuberculosis complex and some related bacteria. It is encoded within the RD1 genomic region and is considered a key virulence determinant in these organisms.

The ESX-1 locus comprises a cluster of genes including esxA and esxB, which encode the secreted proteins ESAT-6 and CFP-10, respectively, as well as a set of components involved in the secretion apparatus (such as eccA1, eccB1, eccC1, eccD1, eccE1, and espA-D). ESAT-6 and CFP-10 are secreted as a heterodimer and are among the best-characterized substrates of the system. The locus and its substrates are highly conserved in pathogenic strains and are absent in the BCG vaccine strain, which contributed to its attenuation.

Functionally, ESX-1 mediates the translocation of effector proteins across the mycobacterial cell envelope, enabling disruption of the phagosomal membrane, escape into the host cell cytosol, and modulation of host immune responses. This activity supports intracellular survival and contributes to tissue pathology observed during infection. In experimental models, mutations that disrupt ESX-1 components or secretion typically result in markedly reduced virulence and impaired replication.

In clinical and research contexts, ESX-1 is a major focus due to its central role in virulence and host–pathogen interactions. Its absence in BCG underpins vaccine attenuation, while understanding ESX-1 mechanisms informs efforts to develop vaccines, diagnostics, and therapeutics targeting tuberculosis and related diseases. ESX-1 is part of a broader family of type VII secretion systems present in actinobacteria.