Computers used to deal with drug-resistant TB

TUBERCULOSIS (TB) is one of the leading causes of death from infectious diseases. Globally, it accounts for 1.3 million deaths and 10.4 million people develop the disease every year.

The standard first-line treatment regimen used for newly diagnosed TB patients involves taking four different drugs over six months. Some patients experience varying degrees of adverse reactions. These factors have led to patients defaulting on their treatment. This, in turn, has led to a rise in drug resistance.

TB drug resistance – when the bacteria become resistant to at least one anti-tb drug – is a growing problem globally. Current treatments that include more than one drug, known as combination therapy, have become inadequate because the bacteria have devised ways to survive even when antibiotics are used.

An estimated 3.5% of new cases and 18% of previously-treated cases of TB are drug-resistant.

There is, therefore, still a need to identify alternative drugs. But the drug discovery process is fairly lengthy (10 to 15 years). This can be shortened with the aid of computers.

To find ways of overcoming the problem, my colleagues and I at the SA National Bioinformatics Institute and School of Pharmacy at the University of the Western Cape used computer strategies to identify alternative drugs. The results were published in Plos One journal.

Our research presents a cost-effective alternative way to tackle drug resistance by identifying drugs that prevent the bacteria from overcoming drug pressure. Using computer modelling, we were able to identify new drugs by building a reliable replica of the bacterial protein and then working out what the best orientation is for the drug to fit in the bacterial protein.

Ongoing studies using a combination of drugs will examine the effect of the drugs on stopping the growth of the bacterium. This, in turn, could lead to a new drug being included in the treatment regimen to beat drug-resistant TB.

One way the bacteria is able to survive drug pressure is by making proteins which mitigate the effect of the drug, such as pumping the drugs out of the cell. Because some antibiotics are only effective when they are inside the bacterial cell, they become ineffective treatments.

The proteins that play this role, called efflux pumps, are important targets in the drug discovery process. But it has been a struggle to identify drugs that can withstand the effect of the efflux pumps.

Using computer modelling, we aimed to identify a drug that binds to the efflux pump protein. | The Conversation