This project comprises an epidemiological arm, for which TB patient are prospectively recruited in the country of Georgia, as well as an experimental arm, mainly carried out in our laboratory in Switzerland.
With regards to the epidemiological arm, after an initial delay due to the COVID-19 pandemic, patient recruitment started in January 2021 and is now well underway. In parallel, clinical information and many microbiological samples are being collected from these TB patients as they are being treated and analyzed in the laboratory in Georgia. A subset of these samples are also sent to Switzerland for more in-depth microbiological and genomic analyses. This epidemiological arm of the project also builds on, and further expands our previous work in Georgia, which studied the transmission of MDR-TB in particular. In terms of results so far, our molecular epidemiological investigations revealed that while some drug-resistant Mtb strains circulating in Georgia are less likely to successfully transmit from patient to patient, other Mtb strains that carry so-called compensatory mutations transmit much better, and in some cases equally well as fully drug-susceptible strains. Moreover, our analyses revealed that prisons have played an important role in the epidemiology of MDR-TB in Georgia, as they might serve as incubators for highly drug-resistant and highly transmissible Mtb strains that subsequently can spill over into the general population. Taken together, these findings have important implications for the control of TB, particularly in light of the ongoing roll-out of the new TB treatment regimens against MDR-TB in Georgia and many countries around the world.
Regarding the experimental arm of the project, we have made progress in setting up a new proteomics pipeline to study the gene expression of defined drug-resistant mutants of Mtb as well as clinical Mtb strains from Georgia. The goal of this work is to explore the physiological effects of different drug resistance mutations, alone and in combinations, on the gene (i.e. protein) expression of these Mtb strains. Similarly, we have successfully established a drug tolerance assay to explore the role of this phenomenon in the evolution of drug resistance in Mtb, including during individual patient treatment. We are now in the process of applying these assays to a large number of Mtb mutants and clinical Mtb strains from Georgia.
