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Early secreted antigenic target 6 kDa and 10-kDa culture filtrate protein complex (ESAT-6/CFP-10)

Target
ESAT-6/CFP-10
Molecular classification
Bacterial effector protein, Antigen, Virulence factor
01

Overview

The Early secreted antigenic target 6 kDa (ESAT-6) and 10-kDa culture filtrate protein (CFP-10) complex is a potent heterodimeric virulence factor secreted by Mycobacterium tuberculosis via the ESX-1 Type VII secretion system (UniProt P9WNK7, P9WNK5). These proteins are encoded within the Region of Difference 1 (RD1), a genomic segment present in virulent M. tuberculosis but notably absent in the attenuated Mycobacterium bovis BCG vaccine strain and most non-tuberculous mycobacteria (Brodin et al., 2004). The complex functions primarily by disrupting host phagosomal membranes, facilitating the escape of the bacteria into the host cell cytosol and modulating immune signaling to favor bacterial persistence (De Leon et al., 2012; PubMed: 17464067). Because of its high immunogenicity and absence in the BCG strain, the ESAT-6/CFP-10 fusion or complex is a cornerstone for diagnostic Interferon-Gamma Release Assays (IGRAs), such as QuantiFERON-TB Gold, which differentiate between TB infection and prior BCG vaccination (CDC, 2021). Furthermore, this protein complex is a primary target for novel recombinant subunit vaccines, including GamTBvac and the H-series (H1, H56) candidates, currently under investigation to improve global tuberculosis control (ClinicalTrials.gov NCT04975763; WHO TB Vaccine Pipeline).

Other names
EsxA/EsxB complexESAT-6/CFP-10 fusion proteinEarly secretory antigenic target-6/Culture filtrate protein-10RD1-encoded antigen complexESAT6-CFP10
02

Mechanism of action

Induction of antigen-specific T-cell mediated immune response, primarily through the stimulation of interferon-gamma (IFN-g) production for diagnostic detection or vaccine-mediated protection.

03

Biological functions

Phagosomal membrane disruptionVirulenceHost immune modulationT-cell activationSecreted effector
04

Disease associations

InfectionTuberculosis
05

Safety considerations

Injection site reactionsPotential for inflammatory responses in active TB casesLimited efficacy in immunocompromised individuals
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Interacting drugs

GamTBvac

6 more in the full profile.

07

Biomarkers

Interferon-gamma (IFN-gamma)T-cell count (via ELISPOT)Skin test induration (for recombinant skin tests)

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