Beta-lactams for Tuberculosis Treatment
The overarching goal of the proposed research was to provide high quality molecular and pharmacodynamic pre-clinical data of selected BLMs alone and in combination to inform future and on going TB clinical trials on the evaluation of BLMs. This goal was structured in two focused questions: (i) which BLMs to use and how to combine them in an optimal BLM-containing TB regime to shorten the duration of TB therapy, prevent relapse and treat M(X)DR-TB and; (ii) understanding the underlying molecular mechanism of the interactions between BLMs and their synergistic partners.
Thanks to this project we have now a clearer view from an in vitro perspective of optimal synergistic companion partners for beta-lactams. We have also addressed the synergistic interaction of rifampicin and several beta-lactams from a molecular perspective and have identified underlying molecular determinants explaining this interaction, something never reported to date. In addition, we have developed a new technology that allows the analysis of drug combinations in vitro in a more dynamic way than standard currently used assays. This new technology has the potential to revolutionize the way new regimens for TB therapy are screened and evaluated at the in vitro level. Finally, we have translated this knowledge to propose a new therapy for Buruli ulcer (BU), a disease difficult to manage in rural areas of Africa. Our findings might improve the life of patients afflicted by this very much-neglected disease by reducing a lengthy 8-week treatment by a shorter 4-week therapy.