Vitamin B2 as a virulence factor in Pseudogymnoascus destructans skin infection
Jazyk angličtina Země Anglie, Velká Británie Médium electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
27620349
PubMed Central
PMC5020413
DOI
10.1038/srep33200
PII: srep33200
Knihovny.cz E-zdroje
- MeSH
- Ascomycota klasifikace genetika patogenita MeSH
- buněčná adheze MeSH
- Chiroptera mikrobiologie MeSH
- dermatomykózy mikrobiologie MeSH
- elektronová mikroskopie MeSH
- faktory virulence metabolismus MeSH
- fibroblasty cytologie metabolismus mikrobiologie MeSH
- fylogeneze MeSH
- interakce hostitele a patogenu MeSH
- křídla zvířecí cytologie mikrobiologie ultrastruktura MeSH
- kultivované buňky MeSH
- membránový potenciál mitochondrií MeSH
- riboflavin metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- faktory virulence MeSH
- riboflavin MeSH
Pathogenic and non-pathogenic related microorganisms differ in secondary metabolite production. Here we show that riboflavin overproduction by a fungal pathogen and its hyperaccumulation in affected host tissue exacerbates a skin infection to necrosis. In white-nose syndrome (WNS) skin lesions caused by Pseudogymnoascus destructans, maximum riboflavin concentrations reached up to 815 μg ml(-1), indicating bioaccumulation and lack of excretion. We found that high riboflavin concentrations are cytotoxic under conditions specific for hibernation, affect bats' primary fibroblasts and induce cell detachment, loss of mitochondrial membrane potential, polymerization of cortical actin, and cell necrosis. Our results explain molecular pathology of WNS, where a skin infection becomes fatal. Hyperaccumulation of vitamin B2 coupled with reduced metabolism and low tissue oxygen saturation during hibernation prevents removal of excess riboflavin in infected bats. Upon reperfusion, oxygen reacts with riboflavin resulting in dramatic pathology after arousal. While multiple molecules enable invasive infection, riboflavin-associated extensive necrosis likely contributes to pathophysiology and altered arousal pattern in infected bats. Bioaccumulation of a vitamin under natural infection represents a novel condition in a complex host-pathogen interplay.
Department of Cell Biology Faculty of Science Charles University Prague Czech Republic
Institute of Vertebrate Biology Academy of Sciences of the Czech Republic Brno Czech Republic
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