Our study goal was to evaluate a set of nutritional indicators among adults with confirmed or suspected active tuberculosis disease in southern India, given the limited literature on this topic. Study objectives were to assess the: I) double burden of malnutrition at individual and population levels; II) relative performance of…
Published Mycobacterium tuberculosis β-ketoacyl-ACP synthase KasA inhibitors lack sufficient potency and/or pharmacokinetic properties. A structure-based approach was used to optimize existing KasA inhibitor DG167. This afforded indazole JSF-3285 with a 30-fold increase in mouse plasma exposure. Biochemical, genetic, and X-ray studies confirmed JSF-3285 targets KasA. JSF-3285 offers substantial activity in…
Cellular bioenergetics is an area showing promise for the development of new antimicrobials, antimalarials and cancer therapy. Enzymes involved in central carbon metabolism and energy generation are essential mediators of bacterial physiology, persistence and pathogenicity, lending themselves natural interest for drug discovery. In particular, succinate and malate are two major…
In 2017 over 550,000 estimated new cases of multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) occurred, emphasizing a need for new treatment strategies. Linezolid (LZD) is a potent antibiotic for drug-resistant Gram-positive infections and is an effective treatment for TB. However, extended LZD use can lead to LZD-associated host toxicities, most commonly bone…
Pulmonary tuberculosis (PTB) is associated with many forms of chronic lung disease including the development of chronic airflow obstruction (AFO). However, the nature, evolution and mechanisms responsible for the AFO after PTB are poorly understood. The aim of this study was to examine the progression of changes in lung physiology…
Tuberculosis represents a major global health problem for which improved approaches are needed to shorten the course of treatment and to combat the emergence of resistant strains. The development of effective and safe nanobead-based interventions can be particularly relevant for increasing the concentrations of antitubercular agents within the infected site…
Doxycycline, an FDA-approved tetracycline, is used in tuberculosis models for the temporal control of mycobacterial gene expression. In these models, animals are infected with recombinant carrying genes of interest under transcriptional control of the doxycycline-responsive TetR- unit. To minimize fluctuations of plasma levels, doxycycline is usually administered in the diet.
Tuberculosis (TB) remains the leading cause of death from an infectious disease worldwide. TB therapy is complicated by the protracted treatment regimens, development of resistance coupled with toxicity and insufficient sterilizing capacity of current drugs. Although considerable progress has been made on establishing a TB drug pipeline, the high attrition…
