Target intelligence / Profile preview

Mycobacterium tuberculosis antigen 85A (Ag85A)

Target
Ag85A
Molecular classification
Enzyme, Acyltransferase, Mycolyltransferase, Fibronectin-binding protein
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Overview

Mycobacterium tuberculosis antigen 85A (Ag85A) is a major secreted protein of the Ag85 complex, which also includes Ag85B and Ag85C. It functions as a mycolyltransferase essential for the synthesis of trehalose dimycolate (TDM), also known as cord factor, which is a vital component of the mycobacterial cell wall and a key virulence factor helping the bacterium maintain structural integrity [1, 4, 15]. Beyond its role in the cell wall, Ag85A possesses diacylglycerol acyltransferase activity involved in the formation of lipid storage bodies that facilitate bacterial survival during dormancy and persistent infection [6, 10, 19]. Due to its high immunogenicity, Ag85A is a primary target for new-generation tuberculosis vaccines, such as the recombinant viral vector MVA85A, which was designed to boost BCG-induced immunity [7, 11, 14]. It is also being explored as a therapeutic target for small-molecule inhibitors and repurposed drugs intended to disrupt mycolic acid metabolism, particularly against multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis strains [15, 16]. Understanding the dual enzymatic and immunological properties of Ag85A is central to developing more effective countermeasures against the global tuberculosis epidemic [3, 13].

Other names
fbpASecreted antigen 85AMycolyltransferase Ag85AFibronectin-binding protein AAntigen 85 complex A
02

Mechanism of action

Ag85A serves as an immunogen in vaccine formulations to elicit protective T-cell immunity and as an enzymatic target for small-molecule inhibitors that block its mycolyltransferase activity, leading to the disruption of cell wall integrity and trehalose dimycolate (TDM) synthesis.

03

Biological functions

Cell wall biosynthesisLipid metabolismCell adhesionImmune response inductionOther
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Disease associations

InfectionTuberculosis
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Safety considerations

Lack of clinical efficacy in specific populations (e.g., infants in MVA85A efficacy trials)Challenges in achieving therapeutic concentrations within mycobacterial granulomasPotential for antibiotic resistance development
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Interacting drugs

MVA85A

6 more in the full profile.

07

Biomarkers

Interferon-gamma (IFN-g)Ag85A-specific CD4+ T cellsAg85A-specific CD8+ T cells

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