Role of the Major Antigen of Mycobacterium tuberculosis in Cell Wall Biogenesis

Abstract

The dominant exported proteins and protective antigens ofMycobacterium tuberculosis are a triad of related gene products called the antigen 85 (Ag85) complex. Each has also been implicated in disease pathogenesis through its fibronectin-binding capacities. A carboxylesterase domain was found within the amino acid sequences of Ag85A, B, and C, and each protein acted as a mycolyltransferase involved in the final stages of mycobacterial cell wall assembly, as shown by direct enzyme assay and site-directed mutagenesis. Furthermore, the use of an antagonist (6-azido-6-deoxy-α,α′-trehalose) of this activity demonstrates that these proteins are essential and potential targets for new antimycobacterial drugs.