The viability of Mycobacterium tuberculosis (Mtb) depends on energy generated by its respiratory chain. Cytochrome bc1-aa3 oxidase and type-2 NADH dehydrogenase (NDH-2) are respiratory chain components predicted to be essential, and are currently targeted for drug development. Here we demonstrate that an Mtb cytochrome bc1-aa3 oxidase deletion mutant is viable and…
Central nervous system tuberculosis (TB) is devastating and affects vulnerable populations. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculous meningitis (TBM) specifically are nearly uniformly fatal, with little information being available to guide the treatment of these patients. Delamanid (DLM), a nitro-dihydro-imidazooxazole, is a new, well-tolerated anti-TB drug with a low…
In HIV hyperendemic sub-Saharan African communities, particularly in southern Africa, the likelihood of achieving the Sustainable Development Goal of ending the tuberculosis (TB) epidemic by 2030 is low, due to lack of cost-effective and practical interventions in population settings. We used one of Africa’s largest population-based prospective cohorts from rural…
Indole-2-carboxamide derivatives are inhibitors of MmpL3, the cell wall-associated mycolic acid transporter of In the present study, we characterized indoleamide effects on bacterial cell morphology and reevaluated pharmacokinetics and efficacy using an optimized oral formulation. Morphologically, indoleamide-treated cells demonstrated significantly higher numbers of dimples near the poles or septum, which…
Current treatments for Mycobacterium tuberculosis infections require long and complicated regimens that can lead to patient non-compliance, increasing incidences of antibiotic-resistant strains, and lack of efficacy against latent stages of disease. Thus, new therapeutics are needed to improve tuberculosis standard of care. One strategy is to target protein homeostasis pathways…
Tuberculosis is the leading cause of death by an infectious disease worldwide. However, the involvement of innate lymphoid cells (ILCs) in immune responses to infection with Mycobacterium tuberculosis (Mtb) is unknown. Here we show that circulating subsets of ILCs are depleted from the blood of participants with pulmonary tuberculosis and…
Bacterial persisters are a subpopulation of cells that exhibit phenotypic resistance during exposure to a lethal dose of antibiotics. They are difficult to target and thought to contribute to the long treatment duration required for tuberculosis. Understanding the molecular and cellular biology of persisters is critical to finding new tuberculosis…
