Young children with exposure to or infection with are at high risk of developing tuberculosis disease, and postexposure tuberculosis preventive treatment decreases this risk. Evidence is limited regarding the dosing and safety of the 12-dose once-weekly rifapentine and isoniazid regimen (3HP) for tuberculosis preventive treatment in children younger than 2…
The GID/CTLH E3 ligase complex is implicated in several biological processes, yet its full substrate repertoire remains poorly defined. We recently identified the complex as a broad modulator of macrophage responses to Mycobacterium tuberculosis (Mtb) infection. Here, we use label-free proteomics and diGly capture analysis of Mtb-infected macrophages to define…
Preclinical tuberculosis (TB) drug evaluation relies heavily on mouse infection models. Drug efficacy varies depending on inoculum and the timing of treatment initiation. These differences reflect, in part, physiological adaptations of () to host immune pressure. We used novel molecular markers of pathogen health (RS ratio and SEARCH-TB) to contrast…
The epidemiology of tuberculosis in Taiwan has been influenced by the introduction of multiple Mycobacterium tuberculosis lineages and by the ageing of the population. We conducted a population-based study to investigate M tuberculosis transmission in Kaohsiung, a city in southern Taiwan.
Treatment optimization through pharmacokinetic evaluation is needed to improve outcomes in tuberculous meningitis (TBM). Clinical assessment of drug penetration into the central nervous system (CNS) is limited to cerebrospinal fluid (CSF) sampling, which may not reflect drug exposures at the site-of-disease. We characterized the pharmacokinetics of antituberculosis drugs in CNS…
Developing tuberculosis drug regimens requires coordinated discovery of multiple, mechanistically distinct agents, which challenge traditional single-asset models. The Tuberculosis Drug Accelerator (TBDA) was established as a multi-organizational consortium to enable collaborative discovery across academia, industry and research institutions. Over more than a decade, the TBDA has demonstrated how such collaborations…
Alveolar macrophages are the first immune cells to encounter Mycobacterium tuberculosis (Mtb) in the lungs, but they frequently fail to eliminate this pathogen, allowing Mtb to persist and replicate. Interstitial macrophages (IMs) are enlisted to restrict bacterial growth and limit immune evasion. While IMs have been implicated in controlling acute…
Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) infection and defined by formation of granulomas, immune aggregates that can restrict or support bacterial replication. Macrophages are fundamental components of granulomas and TB pathogenesis, yet their population structure and functional diversity is incompletely understood. The interaction between macrophages and Mtb in…
