By its very nature, multidrug-resistant tuberculosis (MDR TB), including extensively drug-resistant tuberculosis (XDR TB), is becoming increasingly difficult to treat, so researchers are using genome data to develop compounds that will combat the disease.
According to Dr Ruben Cloete of the South African National Bioinformatics Institute (Sanbi) at the University of the Western Cape, 10% of infected individuals have the latent form of mycobacterium tuberculosis
, which could become active later in life. This makes the discovery of novel compounds very important to reduce the critical reservoir of potential cases of TB.
Understanding the mechanisms of drug resistance
The Christoffels Laboratory at Sanbi is collaborating with the Division of Molecular Biology and Human Genetics in the Faculty of Medicine and Health Sciences at Stellenbosch University to analyse M.tuberculosis
genomic data to understand mechanisms of drug resistance. According to Professor Alan Christoffels, these insights will lead to better drug target identification and ultimately improve drug discovery.
The computational drug discovery platform started with Cloete’s PhD thesis and prioritises nine targets in the M.tuberculosis genome. This work was used to leverage funding from the Technology Innovation Agency to buy computationally identified compounds for ongoing experimental testing against M.tuberculosis at the University of Stellenbosch Medical School.
The drug discovery platform has expanded to include another PhD student, Anati Nkaule, who is interested in the use of computational methods to filter potential drugs as therapeutics against M.tuberculosis
. A second postdoctoral researcher, Dr Mohammed Shabaaz, joined the team in June 2017.
The research to date has fuelled collaboration with the Seattle Structural Genomics Center to determine the 3-D protein structures of the newly prioritised drug targets, as well as the search for efflux pump inhibitors with the School of Pharmacy at the University of the Western Cape.
The work is funded through the DST/NRF Research Chair in Bioinformatics and Public Health Genomics and the Medical Research Council Bioinformatics Unit at Sanbi.