Hosting the highest biodiversity of any biome on Earth, tropical rainforests may represent a goldmine of “bioactive” compounds- medicinal chemicals produced naturally by plants, insects and microorganisms. Given a full 50% of all medicines introduced between 1981 and 2006 came directly from nature, the notion of “bioprospecting”, or combing the diversity of tropical forests for new drugs, has enticed imaginations for decades. But Big Pharma’s interest in bioprospecting has waned in recent decades due to the slow pace of discovery. However, hope is still alive amongst microbiologists working in the field. And for good reason. In a study published last week in the journal PLOS ONE, scientists report on a new, highly promising source of bioactive compounds from a rather unusual suspect: the three toed sloth.
Sloths host entire ecosystems in their thick, coarse hair, including plants (green algae), arthropods (cockroaches, moths and roundworms), bacteria and fungi. Microbiologist Sarah Higgingbotham at the Smithsonian Tropical Research Institute in Panama was interested in finding out whether any of this diversity was medicinally valuable. Of particular interest to Higgingbotham and colleagues were the numerous species of fungi living in sloth hair. Fungi have made substantial contributions to the pool of natural drug products since the discovery of penicillin over 80 years ago.
To uncover potential drug-producing fungi, Higgingbotham and colleagues collected samples of the coarse, outer hair from nine unsuspecting three toed sloths found moseying along a road in Soberanía National Park, Panama (yes, aspiring microbiologists, this is something you can actually get paid to do). The hair samples were taken back to their lab, incubated on petri dishes, and checked regularly for fungal growth. Following growth, the researchers collected fungal hyphae from the plates, extracted and sequenced their DNA in order to determine identity. In total, 84 unique fungi were isolated. Although these fungi are a highly diverse group, including several potentially novel species, most fell into the taxonomic class Sordariomycetes – a well documented source of bioactive compounds.
Samples of 70 isolated fungal strains were grown in liquid culture media and tested for “bioactivity” against malaria, Chagas disease and the breast cancer cell line MCF-7, in addition to 15 human pathogenic bacteria. A strain was considered “highly bioactive” if it inhibited growth of a disease by 50% or more. For 50 of these strains, the researchers also constructed “antibiotic activity profiles” – scorecards indicating the degree to which a given fungal strain inhibits a range of bacterial pathogens. Antibiotic activity profiles are commonly used in medicine to determine the efficacy of a particular drug against an infection. Creating antibiotic activity profiles allows scientists to compare novel antibiotics to databases of antibiotics currently on the market and identify new disease-fighting drugs.
Overall, two of the fungal isolates were highly bioactive against the malaria parasite Plasmodium falciparum and eight were active against the Chagas parasite Trypanosoma cruzi. Fifteen fungal isolates were highly active against the MCF-7 cell line. Bioactivity against T. cruzi is particularly rare and represents a promising alternative to the two currently used drugs, nitrofurane and benznidazole, both of which can have toxic side effects.
Twenty of the fifty fungal isolates screened were bioactive against at least one bacterial pathogen. An exceptionally promising isolate, Lasiodiplodia sp.1, aggressively reduced the growth of several pathogenic Gram-negative bacteria. Infections caused by multi drug-resistant (MDR) Gram-negative bacteria, such as E.coli and Pseudomonas aeruginosa, are on the rise worldwide due to the overuse of antibiotics in hospitals and clean rooms. There is currently a paucity of drugs in development against MDR Gram-negative bacteria compared with their Gram-positive counterparts. Lasiodiplodia’s bioactivity profile did not match that of any known antibiotics, suggesting a potentially novel disease-fighting mechanism.
Twenty nine of the fungal strains isolated by Higgingbotham and colleagues are known endophytes– fungi that make a home living on plants. Endophytic rainforest fungi have recently made news for other remarkable metabolic features such as the capacity to metabolize plastic . The discovery of endophytic fungi on sloth hair increases our understanding of the habitat range occupied by these diverse organisms. Higgingbotham speculates some her fungi living may be associated with the algae present in sloth hair, forming a symbiosis analogous to that seen in lichen.