· The microplate Alamar Blue assay (MABA), currently the most widely used assay for TB drug discovery was developed in the Director’s previous lab and we continue to make minor improvements. In addition we have developed recombinant strains of M. tuberculosis expressing green fluorescent or luciferase proteins that are also used in rapidly assessing activity of candidate drugs. We recently developed the only high throughput-compatible assay for detection of activity against non-replicating M. tuberculosis. This Low Oxygen Recovery Assay (LORA) has the potential to identify compounds that may help reduce the duration of TB treatment. We conduct this assay in our internal projects, our external collaborations as well in our capacity as an NIH (sub)contractor.
· On-going projects include those aimed at developing higher throughput and/or more rapid assays for the determination of activity of compounds in TB-infected macrophages and mice. These involve both genetic manipulation of M. tuberculosis as well as GC or LC/MS based measurements of TB-specific markers.
· We are involved in a collaborative project with Colorado State U. funded by the Gates Foundation to analyze existing anti-TB assays and to make recommendations to the global TB drug discovery community based on these analyses.
· Very recently the ITR has begun to develop an assay that links liver enzyme metabolism with anti-TB activity such that we could rapidly identify active metabolites. This holds promise for not only identifying active metabolites of new, novel anti-TB agents early in the drug discovery process but also of identifying active metabolites of inactive parent compounds during high throughput screening.
