White-nose syndrome (WNS) is a devastating disease of hibernating bats caused by the fungus Pseudogymnoascus destructans. We obtained 383 fungal and bacterial isolates from the Soudan Iron Mine, an important bat hibernaculum in Minnesota, then screened this library for antifungal activity to develop biological control treatments for WNS. An extract from the fungus Oidiodendron truncatum was subjected to bioassay-guided fractionation, which led to the isolation of 14 norditerpene and three anthraquinone metabolites. Ten of these compounds were previously described in the literature, and here we present the structures of seven new norditerpene analogues. Additionally, this is the first report of 4-chlorophyscion from a natural source, previously identified as a semisynthetic product. The compounds PR 1388 and LL-Z1271α were the only inhibitors of P. destructans (MIC = 7.5 and 15 μg/mL, respectively). Compounds were tested for cytotoxicity against fibroblast cell cultures obtained from Myotis septentrionalis (northern long eared bat) and M. grisescens (gray bat) using a standard MTT viability assay. The most active antifungal compound, PR 1388, was nontoxic toward cells from both bat species (IC50 > 100 μM). We discuss the implications of these results in the context of the challenges and logistics of developing a substrate treatment or prophylactic for WNS.
Bibliographical noteFunding Information:
This work was funded by grant ML 2016 Chp 186, sec 2, from the Environmental and Natural Resources Trust Fund by the State of Minnesota to C.E.S. and R.A.B. and USFW F15AP01056 to C.E.S. and R.A.B. We thank J. Nugent for the human fibroblast cell line culture and G. Krause for assistance with the fungal assays. We are grateful to J. Essig, J. Pointer, and the Soudan Underground Mine State Park staff for facilitating field collections. We thank G. Nordquist for helpful discussions and field assistance and the Minnesota Department of Natural Resources for permits and logistical support.
Copyright © 2020 American Chemical Society and American Society of Pharmacognosy.