Prevention of Multi-Drug Phenotypic Resistance by Targeting Adaptive Mistranslation

Babak Javid of Tsinghua University School of Medicine in China will determine whether drugs that increase the accuracy of protein production in Mycobacterium tuberculosis, which causes TB, can boost the effect of existing TB drugs and thereby shorten the current 6 month treatment period. They hypothesized that resistance to TB drugs is caused in part by the ability of the bacterium to change its proteins by making random errors during their synthesis (known as mistranslation). In Phase I, they proved that this was indeed the case, and performed a screen to identify candidate drugs that improved the accuracy of protein production. In Phase II, they will perform a further screen and test whether the identified compounds can reduce therapy duration in two mouse models of TB infection.