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.

• 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