Dormant bacteria II

Thursday, August 21th, 2008 by hinrich

Just a few days ago I have written about our recent publication showing a further reduction of available energy to dormant Mycobateria when treating them with TMC207/R207910. In the most recent edition of PNAS from August 19, another publication by Rao et al. underlines this finding.

The authors of the article have studied the mechanisms by which the bacterium provides itself with energy in the form of ATP. In one of their experiments they monitored the decrease in ATP as the concentration of oxygen was reduced in the environment. In the end, the authors saw 5-fold less ATP in hypoxic (little oxygen available) non-replicating Mycobacteria when compared to growing aerobic (normal oxygen levels) Mycobacteria. These smaller levels of ATP could be further reduced when the bacteria were exposed to increasing levels of TMC207/R207910. Rao et al. highlight that the production of new ATP is essential for the survival of the bacterium in this state. They show that TMC207/R207910 has bactericidal effects on such hypoxic non-replicating Mycobacterium tuberculosis cells.

Researchers currently favor the concept that the presence of the hypoxic non-replicating Mycobacterium tuberculosis bacteria are the reason why the treatment of patients is so lengthy. These bacteria are also viewed as causing the wide-spread latent infection with Mycobacterium tuberculosis. Therefore, if all clinical studies continue to be successful and no serious adverse effects were to be seen in patients, this compound clearly bears the potential to have a profound influence on treating tuberculosis.

You can read the abstract of the paper "The protonmotive force is required for maintaining ATP homeostasis and viability of hypoxic, nonreplicating Mycobacterium tuberculosis" by Rao et al. here.

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