Peat Bog Fungi as a Reservoir of Anti-Tuberculosis Compounds

An analysis of fungi collected from peat bogs has revealed several species that produce substances toxic to the bacterium responsible for tuberculosis in humans.

The results indicate that focusing on bacterial biological processes that support the maintenance of thiol levels may be a promising avenue for the development of more effective treatments. These results are presented by Neha Malhotra of the National Institutes of Health, US, and associates in the journal PLOS Biology.

Even though tuberculosis is preventable and curable, millions of people worldwide contract the disease each year, and over a million of them pass away. However, because the treatment necessitates taking antibiotics every day for months, which can be very difficult, there is an urgent need for new treatments that can shorten the duration of treatment.

Malhotra and associates investigated possible targets for treatment-shortening techniques in sphagnum peat bogs. Numerous species of bacteria belonging to the Mycobacterium genus, including the bacterium that causes tuberculosis, are found in these freshwater wetlands.

Fungi and mycobacteria compete for growth in these bogs' decomposing “gray layer,” which is acidic, nutrient-poor, and oxygen-poor, much like the lesions seen in TB patients' lungs.

Together with each of the roughly 1,500 fungal species that were taken from the gray layer of multiple peat bogs in the northeastern United States, the researchers cultivated Mycobacterium tuberculosis in the lab.

They discovered five fungi that were toxic to the bacteria. These effects were reduced to three distinct compounds patulin, citrinin, and nidulalin A produced by the various fungi through additional laboratory testing.

Each of the three substances seems to have a toxic effect on the TB bacterium by seriously impairing the cellular levels of a class of substances called thiols, some of which are crucial for the molecular functions that keep bacterial cells alive.

According to the researchers, the three compounds themselves are not likely to make good drug candidates. However, the results support a specific approach for developing treatment-shortening medications: focusing on the biological mechanisms that sustain thiol levels in the tuberculosis bacterium, particularly in light of the similarities between the peat-bog environment and tuberculosis lesions.

The authors added, “Pathogenic mycobacteria, like those causing the human diseases leprosy and tuberculosis, are found in abundance in sphagnum peat bogs where the acidic, hypoxic, and nutrient-poor environment gives rise to fierce microbial competition. We isolated fungi from such bogs and screened for those that competed directly with mycobacteria by co-culture and discovered that these fungi all target the same physiological process in mycobacteria using several chemically distinct mechanisms.”