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Millions of hibernating bats across North America have died from white-nose syndrome (WNS), an emerging disease caused by a psychrophilic (cold-loving) fungus,Pseudogymnoascus destructans, that invades their skin. Mechanisms ofP. destructansinvasion of bat epidermis remain obscure. Guided by our in vivo observations, we modeled hibernation with a newly generated little brown bat (Myotis lucifugus) keratinocyte cell line. We uncovered the stealth intracellular lifestyle ofP. destructans, which inhibits apoptosis of keratinocytes and spreads through the cells by two epidermal growth factor receptor (EGFR)–dependent mechanisms: active penetration during torpor and induced endocytosis during arousal. Melanin of endocytosedP. destructansblocks endolysosomal maturation, facilitatingP. destructanssurvival and germination after return to torpor. Blockade of EGFR abortsP. destructansentry into keratinocytes.
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Activity of bacteria isolated from bats against Pseudogymnoascus destructans in China
Summary White‐nose syndrome, a disease that is caused by the psychrophilic fungusPseudogymnoascus destructans, has threatened several North America bat species with extinction. Recent studies have shown that East Asian bats are infected withP. destructansbut show greatly reduced infections. While several factors have been found to contribute to these reduced infections, the role of specific microbes in limitingP. destructansgrowth remains unexplored. We isolated three bacterial strains with the ability to inhibitP. destructans, namely,Pseudomonas yamanorumGZD14026,Pseudomonas brenneriXRD11711 andPseudomonas fragiGZD14479, from bats in China.Pseudomonas yamanorum, with the highest inhibition score, was selected to extract antifungal active substance. Combining mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy analyses, we identified the active compound inhibitingP. destructansas phenazine‐1‐carboxylic acid (PCA), and the minimal inhibitory concentration (MIC) was 50.12 μg ml−1. Whole genome sequencing also revealed the existence of PCA biosynthesis gene clusters. Gas chromatography‐mass spectrometry (GC‐MS) analysis identified volatile organic compounds. The results indicated that 10 ppm octanoic acid, 100 ppm 3‐tert‐butyl‐4‐hydroxyanisole (isoprenol) and 100 ppm 3‐methyl‐3‐buten‐1‐ol (BHA) inhibited the growth ofP. destructans. These results support that bacteria may play a role in limiting the growth ofP. destructanson bats.
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- Award ID(s):
- 1911853
- PAR ID:
- 10363106
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- Microbial Biotechnology
- Volume:
- 15
- Issue:
- 2
- ISSN:
- 1751-7915
- Format(s):
- Medium: X Size: p. 469-481
- Size(s):
- p. 469-481
- Sponsoring Org:
- National Science Foundation
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Abstract Pathogens with persistent environmental stages can have devastating effects on wildlife communities. White-nose syndrome (WNS), caused by the fungusPseudogymnoascus destructans,has caused widespread declines in bat populations of North America. In 2009, during the early stages of the WNS investigation and before molecular techniques had been developed to readily detectP. destructansin environmental samples, we initiated this study to assess whetherP. destructanscan persist in the hibernaculum environment in the absence of its conclusive bat host and cause infections in naive bats. We transferred little brown bats (Myotis lucifugus) from an unaffected winter colony in northwest Wisconsin to twoP. destructanscontaminated hibernacula in Vermont where native bats had been excluded.Infection withP. destructanswas apparent on some bats within 8 weeks following the introduction of unexposed bats to these environments, and mortality from WNS was confirmed by histopathology at both sites 14 weeks following introduction. These results indicate that environmental exposure toP. destructansis sufficient to cause the infection and mortality associated with WNS in naive bats, which increases the probability of winter colony extirpation and complicates conservation efforts.more » « less
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