The extraordinary biological diversity of tropical forests harbors a rich chemical diversity with enormous potential as a source of novel bioactive compounds. Of particular interest are new environments for microbial discovery. Sloths – arboreal mammals commonly found in the lowland forests of Panama – carry a wide variety of micro- and macro-organisms on their coarse outer hair. Here we report for the first time the isolation of diverse and bioactive strains of fungi from sloth hair, and their taxonomic placement. Eighty-four isolates of fungi were obtained in culture from the surface of hair that was collected from living three-toed sloths (Bradypus variegatus, Bradypodidae) in Soberanía National Park, Republic of Panama. Phylogenetic analyses revealed a diverse group of Ascomycota belonging to 28 distinct operational taxonomic units (OTUs), several of which are divergent from previously known taxa. Seventy-four isolates were cultivated in liquid broth and crude extracts were tested for bioactivity in vitro. We found a broad range of activities against strains of the parasites that cause malaria (Plasmodium falciparum) and Chagas disease (Trypanosoma cruzi), and against the human breast cancer cell line MCF-7. Fifty fungal extracts were tested for antibacterial activity in a new antibiotic profile screen called BioMAP; of these, 20 were active against at least one bacterial strain, and one had an unusual pattern of bioactivity against Gram-negative bacteria that suggests a potentially new mode of action. Together our results reveal the importance of exploring novel environments for bioactive fungi, and demonstrate for the first time the taxonomic composition and bioactivity of fungi from sloth hair.
Despite vast increases in spending on international healthcare over the last 20 years, communicable diseases continue to represent an enormous burden to global health . Chronic infectious illnesses such as malaria and diverse neglected tropical diseases (NTDs) affect millions of people each year, mainly women and children in developing countries . The rapid spread of antibiotic resistance has decreased the arsenal available to treat many infectious diseases, with recent emergence of pandrug resistance yielding illnesses that are recalcitrant to treatment with any known drug . Concurrently non-communicable diseases are rising in incidence compared to communicable diseases: in 2008 cancer was responsible for about 7.8 million deaths (about 13% of all deaths worldwide; ).
Natural products represent one of the most significant sources of new drugs today. Approximately 50% of all medicines introduced between 1981 and 2006 were of natural product origin , with an additional 34 natural product-based drugs launched between 1997 and 2007 . Since the discovery of penicillin over 80 years ago, fungi have contributed enormously to natural product drug discovery, providing a host of invaluable medicines including the β-lactam antibiotics, griseofulvin, cyclosporine, fusidic acid, and lovastatin . However, in recent years the hit-rate for bioactivity from fungi has slowed, possibly pointing to the impending exhaustion of ‘low hanging fruit’ – the easily and frequently accessed fungi such as soil microfungi – as sources of new bioactive metabolites.
Conservative estimates suggest that the total number of fungal species in existence exceeds 5 million, yet fewer than 100,000 fungal species have been described  . This suggests that exploring new environments that may be home to previously undescribed fungi could be extremely productive. For example, recent examination of tropical fungal endophytes has described tropical leaves as a ‘biodiversity hotspot’    that is proving fruitful as a source of new bioactive compounds (see  for a review).
Gloer  proposed that production of secondary metabolites by fungi may be influenced by the selective pressures imparted by other organisms. This suggests that environments where many different species exist in close proximity may have particular potential as sources of bioactive metabolites. One such unexplored environment is the fungal microbiome associated with the coarse, sponge-like hair of the three-toed sloth (Bradypus variegatus), an arboreal mammal commonly found in the lowland tropical forests of Central America.
The coat of three-toed sloths consists of two distinct layers: an inner layer of fine, soft hair close to the skin, and an outer layer of coarse hairs that are oval in cross section and are approximately 0.4 mm wide . These outer hairs carry transverse cracks that are home to an apparently ubiquitous green alga, most commonly of the genus Trichophilus . The alga is popularly thought to provide camouflage for sloths against the mottled background of their habitat, but this has not been confirmed with data. Suutari et al.  suggested that exopolymeric substances produced by the alga might encourage the growth of beneficial bacteria. Sloth hair is commonly home to cyanobacteria and diatoms, as well as a variety of macro-organisms (e.g., cockroaches, roundworms, and moth larvae; ). However, little is known about communities of fungi on sloth hair.
In an effort to uncover new sources of drugs for treating vector-borne diseases, cancer, and bacterial infections, we used a culture-based approach to examine fungal communities associated with the coarse, outer hair of Bradypus variegatus in Panama. Here we report the isolation of fungi with bioactivity against Trypanosoma cruzi, the causal agent of Chagas disease; Plasmodium falciparum, the causal agent of malaria; the human breast cancer cell line MCF-7; and a range of Gram-negative and Gram-positive human pathogenic bacteria. Phylogenetic analyses were used to identify these fungi at a finer and more robust level than is possible using typical database-matching methods alone. Our results suggest that sloth hair is an interesting new source of important bioactive fungi with much scope for exploration of the five other extant sloth species found across the neotropics.