Sloth Hair as a Novel Source of Fungi with Potent Anti-Parasitic, Anti-Cancer and Anti-Bacterial Bioactivity

Abstract

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.

The Evolution of Human Cancer Gene Duplications across Mammals

“…These species are xenarthran mammals which diverged from other eutherians during the early Cenozoic (Meredith et al 2011), making them only very distantly related to rodents and primates. To our knowledge, there has not been any cancer reported in sloths; however, sloth fur carries an anti-cancer fungus (Higginbotham et al 2014).…”

Foliar pathogens are unlikely to stabilize coexistence of competing species in a California grassland

“…), we built phylogenetic trees for groups of OTUs with similar sequences (1–52 isolates per data set) (as described in Higginbotham et al. , Spear ). Because not all sequences mapped onto named fungal species, we assigned each operational species a unique species code (Appendix : Table S3).…”

“…First, we assigned operational taxonomic units (OTUs) by manually editing all reads, automatically assembling bidirectional reads into consensus sequences using a minimum of 20% overlap and 85% sequence similarity, and clustering the 288 consensus sequences and two unidirectional sequences based on a minimum of 40% overlap and 90%, 95%, 97%, and 99% sequence similarity using Sequencher (Gene Codes, Ann Arbor, Michigan, USA). Second, because sequence similarity for the ITS region varies across fungal species (O'Brien et al 2005), we built phylogenetic trees for groups of OTUs with similar sequences (1-52 isolates per data set) (as described in Higginbotham et al 2014, Spear 2017. Because not all sequences mapped onto named fungal species, we assigned each operational species a unique species code (Appendix S1: Table S3).…”

SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents

“…[6,9] An umber of studies have shown ar elationship between cancer and malaria in regard to diagnostics, drug research, treatment, prevention, and epidemiology. [10][11][12][13] Different classes of antimalarial drugs display direct or adjuvant activity against cancer cell lines, are knowna ss ensitivity reversers of resistant tumor cell lines or inhibitors of drug resistance development, or have synergistic action with knowna nticancer drugs. [14][15][16][17][18][19][20] Althought heir exact mode of action against canceri ss till not completely understood,v arious mechanisms have been proposed.…”