To find new treatments for tuberculosis, researchers at the National Institutes of Health’s (NIH's) National Institute of Allergy and Infectious Diseases turned to the natural enemies of the pathogen that causes it: fungi living in peat bogs. Three compounds isolated from tuberculosis’s fungal foes killed cultured cells of the bacterium that causes the disease, Mycobacterium tuberculosis (Mtb), in lab tests.
The results were published in PLOS Biology on Dec. 3.
To find compounds that could kill Mtb, a research team led by the NIH’s Clifton Barry, Ph.D., grew about 1,500 fungi species collected from sphagnum peat bogs in West Virginia and Maine alongside the tuberculosis pathogen. Fungi live in these moss-filled bogs alongside Mtb’s relatives in the Mycobacterium genus, and the microbes compete for the same resources. This cutthroat competition has led fungi to evolve chemical weapons that kill Mycobacterium.
Five of the fungi had a toxic effect on Mtb, with three producing patulin, one citrinin and the other nidulalin A when faced with their bacterial enemy.
Of the three fungal toxins, citrinin showing more modest activity against Mtb compared to the others. All three target chemicals called thiols, including mycothiol, which Mtb uses to protect against oxidative stress. The fact that fungi have evolved different compounds that all go after thiols suggests the defensive pathway might be an Achilles' heel for Mtb, the authors wrote.
Though the authors note that these toxins likely wouldn’t make good drugs themselves, their activity in the thiol pathway suggests potential targets for new tuberculosis drugs, they wrote.
Tuberculosis was tied to 1.25 million deaths in 2023 and has likely retaken the position of world’s deadliest pathogen back from COVID-19, according to the World Health Organization. Current treatments involve antibiotic regimens that take four, six or nine months. Shorter courses of tuberculosis treatment could improve patient adherence and reduce the risk of the bacteria developing drug resistance.