Tuberculosis (TB) remains a leading cause of death due to an infectious agent. Adherence to long and complex TB treatments is supported by methods including directly observed therapy. The negative impact of missed drug doses on clinical outcomes is well established, highlighting both the importance of adherence support and methods…
The development of new regimens to treat tuberculosis (TB), the disease caused by , is critical to improving patient outcomes and decreasing global infectious disease mortality. Early evaluation of candidate regimens in non-clinical models of TB, such as the relapsing mouse model (RMM), remains an important step in prioritizing the…
Early bactericidal activity and time to sputum conversion are well-established study end points in both preclinical animal models and clinical trials for testing drug regimens for pulmonary tuberculosis (TB). The development and optimization of treatment-shortening drug regimens for TB have been challenged by disparities between these study end points and…
Eradication of tuberculosis requires new drugs targeting novel pathways. Although purine metabolism represents an essential antitubercular target, concerns about host nucleobase rescue limited its exploration. New data demonstrate that nucleobase levels in human lung tissue are insufficient to confer rescue, renewing interest in this pathway for tuberculosis drug discovery.
Since the release of the first Mycobacterium tuberculosis genome in 1998, major advances have been made in understanding the biology of this pathogen, the leading infectious cause of death in modern human history. In this Review, we outline the physiological and metabolic features thought to underpin the survival, evasion and…
Multiple studies have reported genes in the M. tuberculosis (Mtb) genome that are under diversifying selection, based on genetic variants among Mtb clinical isolates. These might reflect adaptions to selection pressures associated with modern clinical treatment of TB. Many, but not all, of these genes under selection are related to…
Understanding the functional impact of bacterial genetic diversity is crucial for linking pathogen variants to clinical outcomes. Here, we introduce a high-throughput cytological profiling pipeline optimized for (Mtb) clinical strains, integrating OD-calibrated feature analysis and high-content microscopy. Our system quantifies single-bacterium morphological and physiological traits related to DNA replication, redox…
A key challenge in preclinical tuberculosis drug development is identifying optimal antibiotic combinations. Drug interactions are complex because one drug may affect () physiology in a way that alters the activity of another drug. Conventional pharmacodynamic evaluation based on colony-forming units (CFU) does not provide information about this physiologic interaction…
