Swiss TPH

One of the most important questions in the epidemiology of drug-resistant TB is whether the global burden of drug resistance is primarily due to the de novo acquisition of resistance during patient treatment or a consequence of transmission of already drug-resistant strains. Traditionally, the thought was that drug resistance in bacteria was universally associated with a reduction in virulence and/or transmissibility. However, when reviewing the current evidence for the transmissibility of drug-resistant Mtb, we found that multidrug-resistant strains of Mtb were everything from 10 times less- to 10 times more transmissible than drug-susceptible strains (Figure 1). The reason for this heterogeneity is partially because the molecular basis of drug resistance in Mtb is complex, and different drug resistance-conferring mutations are associated with different effects on strain fitness. Furthermore, by using a combination of experimental evolution and comparative genome sequencing of clinical strains, we have discovered secondary mutations which might mitigate some of the negative effects of the primary drug resistance-conferring mutations in Mtb. Validation of some of these putative fitness-restoring or compensatory mutations is currently on the way.