(Mtb) remains a leading cause of infectious disease mortality worldwide, largely due to its ability to survive within host macrophages. Despite advances in understanding the environmental pressures Mtb encounters , the genetic requirements for adaptation and survival within the intracellular niche remain incompletely defined. Here, we employed a genome-wide…
Despite the approval of two first-in-class anti-tuberculars over the past two decades, the global burden of tuberculosis (TB) remains unacceptably high, in part due to the emergence and spread of drug-resistant strains of Mycobacterium tuberculosis (Mtb). This review summarizes advances and ongoing challenges in anti-TB drug discovery, focusing on identifying…
Post-antibiotic effect (PAE) describes the delay in bacterial growth that continues after antibiotics are cleared. The physiologic basis of PAE in Mycobacterium tuberculosis (Mtb) remains poorly understood. Here, we evaluated the long-standing hypothesis that PAE reflects the time required for bacteria to recover from drug-induced physiologic damage by comparing Mtb…
Controlled human infection models (CHIMs) can accelerate vaccine development for infectious diseases. Mycobacterium tuberculosis is a human-adapted pathogen that is the leading infectious cause of death worldwide. M tuberculosis infection results in a spectrum of clinical outcomes that are incompletely modelled in animals. To date, the risks of infection, prolonged…
Linezolid, an oxazolidinone, is a cornerstone of treatment regimens for highly drug-resistant tuberculosis but cannot be used in drug-susceptible disease because of toxicity. This toxicity results from inhibition of mammalian mitochondrial protein synthesis. Here we show the development of a new oxazolidinone, MK-7762, with antitubercular activity that is better than…
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…
In Tuberculosis Trials Consortium Study 35, which investigated the optimal dosing and safety of once-weekly isoniazid and rifapentine (3HP) in 69 children requiring tuberculosis preventive therapy, 7 children with HIV received 50 mg of once-daily dolutegravir. Plasma dolutegravir concentrations were consistent with those predicted in children on dolutegravir not receiving…
