Fungi from U.S. peat bogs may hold the key to new tuberculosis (TB) treatments, a new study has revealed.
Researchers from the National Institutes of Health have identified fungal compounds that could pave the way for shorter, more effective TB treatments.
The findings, published in the journal PLOS Biology, point to innovative strategies for combating a disease that afflicts millions annually.
Every year, TB infects millions globally, with over 1 million deaths despite the disease being both preventable and curable.
In the US, some 8,000 people were infected with the disease in 2022, with TB coming in behind COVID-19 as the second most infectious killer, according to the American Lung Association.
The number of cases in the U.S. has been steadily declining since 1992 but has increased following the COVID-19 pandemic, according to the latest data from the Centers for Disease Control and Prevention.
Disruptions to health care services and changes in migration travel disruptions were cited as likely contributors to the increase, but the trend highlights the difficulty in eradicating the illness that has blighted societies for centuries.
TB is an infectious disease spread by bacteria affecting the lungs. It's spread through the air when infected patients cough, sneeze or spit.
Existing treatments require months of daily antibiotics, posing significant challenges for patients and healthcare systems. The need for shorter, more manageable therapies is urgent.
The research team turned to sphagnum peat bogs in the northeastern U.S., environments rich with competitive microbial species.
These wetlands mimic conditions found in TB patients' lungs: acidic, low in nutrients, and oxygen-deprived.
This similarity prompted the researchers to investigate how fungi in these bogs fight Mycobacterium species, the same bacterial genus that includes Mycobacterium tuberculosis, which causes TB.
"Fungi have an enormous repertoire of secondary metabolites they can produce and they have had millennia to select which ones are right for the challenge," Clifton Barry, one of the study's authors, told Newsweek.
"In this case, what was amazing was that three unrelated fungi converged on the same solution—they all produce different substances that have the same effect—and they only produce them when they are exposed to Mycobacterium tuberculosis."
In laboratory experiments, the team co-cultured Mycobacterium tuberculosis with 1,500 fungal species collected from the bogs. They identified five fungi with toxic effects on the bacterium, isolating three key compounds: patulin, citrin and nidulalin A.
These substances disrupt thiols—a critical class of molecules essential for bacterial survival.
"These compounds, like most natural products, are not directly useful in humans. They wouldn't be able to be taken orally, for example," Barry said.
"This is not unusual for a natural product starting point for drug discovery; rifampicin, for example, was not useful when it was identified from another bacteria; it took years to convert it into one of the front-line anti-TB drugs in wide use today."
Although these compounds are not suitable as drugs themselves, the discovery offers a promising path forward.
Targeting thiol-regulating processes in TB bacteria could lead to treatment-shortening therapies. The parallels between the bog environment and TB lung lesions strengthen the potential of this approach.
Barry added, "The next steps are to identify compounds that have the same effect but have better pharmaceutical properties (i.e., they can be taken orally, are safe, and can be manufactured at scale). The good news is we already have candidates that hit this same mechanism and are pretty far along the path to human trials."
Is there a health problem that's worrying you? Do you have a question about tuberculosis? Let us know via health@newsweek.com. We can ask experts for advice, and your story could be featured in Newsweek.
Reference
Malhotra N, Oh S, Finin P, Medrano J, Andrews J, Goodwin M, et al. (2024) Environmental fungi target thiol homeostasis to compete with Mycobacterium tuberculosis. PLoS Biol 22(12): e3002852. https://doi.org/10.1371/journal.pbio.3002852
English (US) ·