Antifungal Norditerpene Oidiolactones from the Fungus Oidiodendron truncatum, a Potential Biocontrol Agent for White-Nose Syndrome in Bats

Abstract

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 (IC 50 > 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.

Collective Synthesis and Cytotoxicities of Wentilactone Type Norditerpenoid Dilactones

“… [34] Thus, 3β‐ol 1 was subjected to epimerization; Dess‐Martin oxidation of 1 led to ketone 25 (95%); subsequent reduction with ( i ‐PrO) 3 Al afforded 3α‐ol 26 (75%) [8] . Methylation or acetylation of the resulting hydroxyl group provided 27 and 29 , respectively [35] . Allylic oxidation of 27 and 29 with SeO 2 afforded C14‐hemiacetal 28 and 30 in moderate yields (50%).…”

Development of a multi-year white-nose syndrome mitigation strategy using antifungal volatile organic compounds

“…A number of potential mitigation methods have been developed or experimentally tested against P. destructans or treating white-nose syndrome, including chemical agents [14][15][16][17][18][19][20], microbial antagonists [21][22][23][24][25][26][27], environmental modulation [28,29], UV light exposure [30][31][32], antibiotics [33], vaccination [34], and electrolyte supplementation [35], among others. Of these, the greatest interest has been in the use of chemical and microbial agents to inhibit the growth and pathogenicity of P. destructans.…”

Activity of bacteria isolated from bats against Pseudogymnoascus destructans in China

“…WNS has killed millions of bats in North America from 2006, with several species being severely affected (Frick et al ., 2010 ; Langwig et al ., 2012 ). Bacteria and fungi isolated from bats and the environment have been shown to inhibit the growth of P. destructans in vitro (Hoyt et al ., 2015 ; Raudabaugh and Miller, 2015 ; Micalizzi et al ., 2017 ; Rusman et al ., 2020 ), and application of Pseudomonas fluorescens on bat skin over winter was recently shown to increase survival for one species of bat (Hoyt et al ., 2019 ). P. destructans conidia have also been shown to be inhibited by the volatile organic compounds produced by R. rhodochrous (Cornelison et al ., 2014 ) and trans‐farnesol, a sesquiterpene made by the yeast Candida (Raudabaugh and Miller, 2015 ).…”

“…P. destructans conidia have also been shown to be inhibited by the volatile organic compounds produced by R. rhodochrous (Cornelison et al ., 2014 ) and trans‐farnesol, a sesquiterpene made by the yeast Candida (Raudabaugh and Miller, 2015 ). In addition, Oidiodendron truncatum was shown to produce various compounds that reduced the growth of P. destructans at low concentrations (Rusman et al ., 2020 ). These studies demonstrated that bacteria were likely to contribute to differences in infections among individuals and species in bats.…”