In the 1970s, inclusion of pyrazinamide (PZA) in the drug regimen of tuberculosis (TB) patients for the first 2 mo achieved a drastic reduction of therapy duration. Until now, however, the mechanisms underlying PZA’s unique contribution to efficacy have remained controversial, and animal efficacy data vary across species. To understand…
Metabolism was once relegated to the supply of energy and biosynthetic precursors, but it has now become clear that it is a specific mediator of nearly all physiological processes. In the context of microbial pathogenesis, metabolism has expanded outside its canonical role in bacterial replication. Among human pathogens, this expansion…
The oxazolidinone linezolid is an effective component of drug-resistant TB treatment, but its use is limited by toxicity and the optimum dose is uncertain. Current strategies are not informed by clinical pharmacokinetic (PK)/pharmacodynamic (PD) data; we aimed to address this gap.
Tuberculosis (TB) is the leading infectious cause of death worldwide. A major barrier to control of the pandemic is a lack of clinical biomarkers with the ability to distinguish active TB from healthy and sick controls and potential for development into point-of-care diagnostics.
Genetic deficiency of protein kinase R (PKR) in mice was reported to enhance macrophage activation in vitro in response to interferon-γ (IFNγ) and to reduce the burden of Mycobacterium tuberculosis (Mtb) in vivo (Wu et al. PloS One. 2012 7:e30512). Consistent with this, treatment of wild-type (WT) macrophages in vitro with…
Mycobacterium tuberculosis (Mtb) remains a grave threat to world health with emerging drug resistant strains. One prominent feature of Mtb infection is the extensive reprogramming of host tissue at the site of infection. Here we report that inhibition of matrix metalloproteinase (MMP) activity by a panel of small molecule inhibitors…
Successful drug treatment for tuberculosis (TB) depends on the unique contributions of its component drugs. Drug resistance poses a threat to the efficacy of individual drugs and the regimens to which they contribute. Biologically and chemically validated targets capable of replacing individual components of current TB chemotherapy are a major…
Mycobacterium tuberculosis is an expert and deadly pathogen, causing the disease tuberculosis (TB) in humans. It has several notable features: the ability to enter non-replicating states for long periods and cause latent infection; metabolic remodelling during chronic infection; a thick, waxy cell wall; slow growth rate in culture; and intrinsic…
