Bioactivity of fungal endophytes as a function of endophyte taxonomy and the taxonomy and distribution of their host plants.

Sarah J Higginbotham,Phyllis D Coley,Thomas A Kursar,A Elizabeth Arnold,Alicia Ibañez,Carmenza Spadafora,Jason E Stajich

doi:10.1371/journal.pone.0073192

Abstract

Fungal endophytes – fungi that grow within plant tissues without causing immediate signs of disease – are abundant and diverse producers of bioactive secondary metabolites. Endophytes associated with leaves of tropical plants are an especially exciting and relatively untapped source of novel compounds. However, one major challenge in drug discovery lies in developing strategies to efficiently recover highly bioactive strains. As part of a 15-year drug discovery project, foliar endophytes were isolated from 3198 plant samples (51 orders, 105 families and at least 232 genera of angiosperms and ferns) collected in nine geographically distinct regions of Panama. Extracts from culture supernatants of >2700 isolates were tested for bioactivity (in vitro percent inhibition of growth, % IG) against a human breast cancer cell line (MCF-7) and the causative agents of malaria, leishmaniasis, and Chagas' disease. Overall, 32.7% of endophyte isolates were highly active in at least one bioassay, including representatives of diverse fungal lineages, host lineages, and collection sites. Up to 17% of isolates tested per assay were highly active. Most bioactive strains were active in only one assay. Fungal lineages differed in the incidence and degree of bioactivity, as did fungi from particular plant taxa, and greater bioactivity was observed in endophytes isolated from plants in cloud forests vs. lowland forests. Our results suggest that using host taxonomy and forest type to tailor plant collections, and selecting endophytes from specific orders or families for cultivation, will markedly increase the efficiency and efficacy of discovering bioactive metabolites for particular pharmaceutical targets.

Highlights

Poor nutrition, a lack of clean water and proper sanitation, global climate change, population aging, pollution, and the emergence of drug-resistant pathogens together contribute to the economic and human challenges of today’s global disease burden [1] [2] [3] [4] [5]
Endophytes were isolated from 3198 plant collections representing 51 orders, 105 families and at least 232 genera of angiosperms and ferns collected in national parks throughout Panama
We found that cloud forest endophytes had significantly higher mean % IG than lowland humid forest endophytes against both P. falciparum (F29, 665 = 8.54, p = 0.0001) and L. donovani (F16,931 = 2.07, p = 0.0079) in vitro

Summary

Introduction

A lack of clean water and proper sanitation, global climate change, population aging, pollution, and the emergence of drug-resistant pathogens together contribute to the economic and human challenges of today’s global disease burden [1] [2] [3] [4] [5]. Neglected tropical diseases, including leishmaniasis and Chagas’ disease, have a global disease burden of on par with that of cancer (11.4% of annual deaths), with malaria alone causing an estimated 655,000 deaths in 2008 (mostly of African children) [1] [2] [3]. After peaking during the ‘Golden Age of Antibiotics’ in the first half of the 20th century, the pharmaceutical industry’s interest in natural products and natural product structures as a source of drug leads has gradually decreased [6]. New methods for screening, new approaches for engineering novel products from natural scaffolds, and the emergence of new diseases argue for re-evaluation of drug discovery processes, especially with regard to natural products from under-explored sources [11]. About 8,600 (38%) of these are of fungal origin [10], highlighting the biochemical richness of this diverse clade of eukaryotes

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Conclusion