Little effect of TMC207/R207910 in the Loebel model

Friday, October 16th, 2009 by hinrich

Structure of TMC207/R207910

Martin Gengenbacher et al. of the Novartis Institute For Tropical Diseases have recently published an article about observations they have made on Mycobacterium tuberculosis bacteria that were cultivated under nutrient deprivation in oxygen-rich medium (Loebel model).

The authors were surprised to see that Mycobacterium tuberculosis cultivated under these conditions were not affected by TMC207/R207910. As the compound is inhibiting the ATP synthase it is puzzling that viability was not affected and the intracellular levels of ATP were only slightly reduced.

While it is disappointing to see limited efficacy of TMC207/R207910 in the Loebel model, the authors of the paper do conclude that ATP level reduction might be an important step in the adaptation of M. tuberculosis to non-growing survival. We will need to look closely at the observations in this paper especially regarding the work that we are doing with TMC207/R207910 in the context of dormant Mycobacterium tuberculosis

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

Posted in Tuberculosis