How broad is the antimycobacterial activity of TMC207/R207910?

Friday, September 11th, 2009 by hinrich

Structure of TMC207/R207910

A new paper by Nacer Lounis et al. published ahead of print in the journal Antimicrobial Agents and Chemotherapy looks into the activity of TMC207/R207910 in Mycobacterium avium. Diseases caused by this bacterium are difficult to treat as M. avium is much less susceptible to most antimicrobial agents than e.g., Mycobacterium tuberculosis. Looking at the high activity of TMC207/R207910 in M. tuberculosis, it would be very beneficial for patients if the compound would also show an effect against Mycobacterium avium.

The paper describes experiments in which groups of mice infected with either of the two Mycobacteria species were treated with the compound. However, it turns out that there is a dramatic difference in efficacy. The in vivo activity of TMC207 against Mycobacterium avium was disappointingly low. The scientists demonstrate a bactericidal activity against Mycobacterium tuberculosis but only a bacteriostatic activity against M. avium.

While this result is disappointing, two questions come to mind: Does the mechanism by which mycobacteria are inhibited in their growth differ from the mechanism by which they are killed? Why are some mycobacteria not killed by TMC207/R207910 while others do get killed?

Please read the article for more detailed information. The abstract can be found here.

Posted in Tuberculosis