Certain populations of Mycobacterium tuberculosis go undetected by standard diagnostics but can be enumerated using limiting dilution assays. These differentially detectable M. tuberculosis (DD M. tuberculosis) populations may have relevance for persistence due to their drug tolerance. It is unclear how well DD M. tuberculosis from patients is modeled by…
The widespread use of antibiotics has placed bacterial pathogens under intense pressure to evolve new survival mechanisms. Genomic analysis of 51,229 ()clinical isolates has identified an essential transcriptional regulator, , herein called for resilience regulator, as a frequent target of positive (adaptive) selection. mutants do not show canonical drug resistance…
Tuberculosis (TB) is an infectious disease bedeviled by complexity. This poses myriad challenges for a research ecosystem organized around specialist host- and/or pathogen-focused thrusts. Here, we highlight the key challenges and their implications for developing new tools to control TB.
The increase of global cases of drug resistant (DR) Mycobacterium tuberculosis (M.tb) is a serious problem for the tuberculosis research community and the goals to END TB by 2030. Due to the need for advancing and screening next generation therapeutics and vaccines, we aimed to design preclinical DR models of…
Despite two decades of intensified research to understand and cure tuberculosis disease, biological uncertainties remain and hamper progress. However, owing to collaborative initiatives including academia, the pharmaceutical industry and non-for-profit organizations, the drug candidate pipeline is promising. This exceptional success comes with the inherent challenge of prioritizing multidrug regimens for…
The unfoldase ClpC1 is one of the most exciting drug targets against tuberculosis. This AAA+ unfoldase works in cooperation with the ClpP1P2 protease and is the target of at least four natural product antibiotics: cyclomarin, ecumicin, lassomycin, and rufomycin. Although these molecules are promising starting points for drug development, their…
