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Inhibitory and synergistic effects of volatile organic compounds from bat caves against Pseudogymnoascus destructans in vitro

Summary

Researchers discovered that two natural compounds found in bat cave environments—isovaleric acid and ethyl methyl carbonate—can effectively kill the fungus that causes white-nose syndrome in bats. When used together, these compounds work even better than alone, disrupting the fungus’s cell membranes, causing it to produce too many reactive molecules (free radicals), and triggering cell death. This discovery offers hope for developing new treatments to protect bat populations that have been devastated by this disease in North America.

Background

White-nose syndrome (WNS) caused by Pseudogymnoascus destructans has devastated bat populations in North America, declining over 90% in some species since 2006. Environmental reservoirs in bat caves may contain volatile organic compounds (VOCs) with antifungal properties that help hosts resist infection. Chinese bat populations remain unaffected by WNS, possibly due to environmental factors and coevolutionary resistance mechanisms.

Objective

This study investigates the antifungal effects of two VOCs isolated from bat cave environments—isovaleric acid (IVA) and ethyl methyl carbonate (EMC)—against P. destructans individually and in combination. The research aims to elucidate the physiological, biochemical, and molecular mechanisms underlying their synergistic antifungal activity.

Results

Both IVA and EMC inhibited P. destructans mycelial growth in a dose-dependent manner with IC₅₀ values of 0.4 μL/mL and 1.52 μL/mL respectively. The IVA-EMC combination exhibited synergistic effects (FICI=0.375) and disrupted cell membrane integrity, elevated ATP and NADPH levels, induced ROS accumulation and apoptosis, and caused DNA damage. Combined treatment upregulated energy metabolism and purine metabolism pathways while downregulating heat shock protein expression.

Conclusion

This study demonstrates that environmental VOCs from bat caves possess significant antifungal potential against P. destructans through multiple mechanisms including membrane disruption, oxidative stress, apoptosis induction, and interference with purine metabolism and cAMP signaling. The findings provide theoretical basis for developing novel, environmentally-derived strategies for preventing and controlling white-nose syndrome.
  • Published in:mSystems,
  • Study Type:In vitro Experimental Study,
  • Source: PMID: 41410543
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