Tackling tuberculosis with garden dirt

Tuberculosis may seem like a disease of yesteryear, but new drug-resistant strains of Mycobacterium tuberculosis are on the rise, with nearly half a million cases a year leading to more than 250,000 deaths.

According to Dr Margaret Chan, director-general of the World Health Organization, “Addressing drug-resistant TB research is a top priority for WHO and for the world. More than US$800 million per year is currently necessary to fund badly needed research into new antibiotics to treat TB.”

Researchers from the University of Sydney have been looking at antibacterial compounds from common garden dirt to synthesise analogues — new compounds with structural variations that have proven effective against drug-resistant TB strains in the lab.

“These analogues inhibit the action of a key protein needed to build a protective cell wall around the bacterium,” said Professor Richard Payne, from the university’s School of Chemistry. “Without a cell wall, the bacterium dies. This wall-building protein is not targeted by currently available drugs.”

Further testing and safety studies are required but it is hoped that these analogues may lead to new, more effective treatments, especially as the analogues “also effectively killed TB-causing bacteria inside macrophages, the cells in which the bacteria live in human lungs”, said Professor Payne.

In recent decades only two new antibiotics with the potential to fight drug-resistant TB have gone through Phase IIB trials, and both are still engaged in Phase III trials. Currently, over 10 million new cases of TB are diagnosed annually with around 1.4 million deaths per year.

The WHO recently published an updated list of antibiotic-resistant pathogens that pose a significant risk to human health. According to WHO Assistant Director-General, Dr Marie-Paule Kieny, TB was not included in this list as “there is already consensus that TB is a top priority for R&D for new antibiotics”.

In November 2017, research into drug-resistant TB will be a major theme at a WHO Ministerial Conference in Moscow.

Published in Nature Communications, Professor Payne’s research was part of an international collaboration that decided to look at soil bacteria compounds as they are known to effectively prevent other bacteria growing around them. Along with Warwick Britton, from the Sydney Medical School and the Centenary Institute, this research utilised the resources of Australia’s National Health and Medical Research Council, Monash University, the University of Queensland, Warwick University (UK), Canada’s Simon Fraser University and Colorado State University.

Image caption: Scanning electron micrograph of Mycobacterium tuberculosis bacteria, which cause tuberculosis. Image courtesy of NIAID under CC BY 2.0