Press release, Ecofect LabEx and Université de Lyon: The study devised by researchers from the International Centre for Infectiology Research (CIRI) and the Biometry and Evolutionary Biology Laboratory (LBBE), funded by the Ecofect LabEx under the EVOFIT-COMBO-TB project, focused on tuberculosis patients who responded slowly to treatment. We performed a genetic characterisation of the clinical isolates of Mtb to look for sub-populations likely to tolerate tuberculosis drugs.
We found that the clinical Mtb isolates obtained from 9/15 patients presenting a delayed response to treatment contained different sub-populations. Additionally, in vitro exposure to a leading tuberculosis drug, rifampicin, revealed Mtb sub-populations in 6/15 isolates, none of which were linked to known drug-resistance mechanisms.
However, exposure to rifampicin revealed sub-populations of Mtb in only 2/20 isolates from the control cohort of patients who responded quickly to treatment. Furthermore, we characterised an Mtb variant isolated from a minority sub-population in the initial clinical isolate, but which became a majority sub-population following in vitro exposure to rifampicin. We found that this variant featured a modified lipid envelope and was able to develop in the presence of RIF and inside human macrophage cells – immune cells that play a central role in controlling Mtb infections. Even more importantly, we performed pharmacological modelling and found that this kind of variant may be related to a poor response to treatment.
To conclude, searching for particular Mtb sub-populations or variants may help identify patients at risk of treatment failure and provide additional guidance for TB management.