Recombinant M. Tuberculosis Rv2253 Antigen [His]

The first asymmetric total synthesis of three structures proposed for mycobacterial diacyl trehaloses, DAT(1), DAT(2), and DAT(3) is reported. The presence of two of these gjycolipids, DAT(1) and DAT(3), within different strains of pathogenic M. tuberculosis was confirmed, and it was shown that their abundance varies significantly. In mass spectrometry, synthetic DAT(2) possessed almost identical fragmentation patterns to presumptive DAT(2) from Mycobacterium tuberculosis H37Rv, but did not coelute by HPLC, raising questions as the precise relationship of the synthetic and natural materials. The synthetic DATs were examined as agonists for signaling by the C-type lectin, Minde. The small differences in the chemical structure of the lipidic parts of DAT(1), DAT(2), and DAT(3) led to drastic differences of Mincle binding and activation, with DAT 3 showing similar potency as the known Mincle agonist trehalose dimycolate (TDM). In the future, DAT(3) could serve as basis for the design of vaccine adjuvants with simplified chemical structure.

Tuberculosis (TB) is a devastating infectious disease that causes a high rate of mortality. Drugs with new modes of action are needed to overcome this scenario. Cationic antibacterial peptides can serve as a potential alternative to existing TB drugs as they target the entire bacterial membrane for activity, thereby reducing the probability of development of drug resistance. In this study, we report anti-tuberculosis activity of B1CTcu5, a peptide that belongs to brevinin-1 family of antimicrobial peptides. This peptide possesses potent in vitro inhibitory activity against M. tuberculosis at 12.5 mu g/mL but was not active against M. smegmatis. B1CTcu5 successfully eliminated intracellular mycobacteria without inducing cytotoxicity to the human macrophages at the concentrations tested. This peptide can be used as a template to design peptide-based anti-tubercular agents.