Project Lead(s): Patrick Arthur
About a million people die annually from tuberculosis (TB).
Almost all the existing TB drugs are being rendered useless, due to drug-resistant TB strains; there is an urgent need to secure new and more effective TB drugs to treat latent and drug-resistant TB.
The proposed approach in the project was to discover new and more effective TB drugs from fungal sources, using an integrated proteomics platform that determines both the mechanism of drug action and resistance.
The aim in this project was to isolate more than 20 new chemical entities to fight drug-resistant TB infections and latent TB.
The long-term goal was to be able to contribute to the reduction of treatment time from the usual 6–12 months of daily antibiotic doses to one month.
A large collection of wood-decaying fungi (WDF) were selected, from which eight different WDF isolates with interesting antimycobacterial activities were selected.
These eight WDF were each cultured in a 10-litre liquid medium.
Isolation of bioactive compounds from extracts with proven activity against S. auerus, E. coli, C. albicans and M. smegmatis was achieved using the whole cell phenotypic screening bioassay-guided fractionation approach.
Proof of concept for this project was partly achieved, as the project team ran out of time to complete the research. They demonstrated that there is specific proteome-wide response in Mycobacteria cells treated with specific antibiotics. They were able to obtain several partially purified bioactive fractions that were active against multiple drug-resistant Mycobacterial cells.
Plans are to apply for Phase II Transition To Scale funding to continue the project.