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A vanillin derivative causes mitochondrial dysfunction and triggers oxidative stress in Cryptococcus neoformans

Cited 28 time in Web of Science Cited 42 time in Scopus
Issue Date
2014-02
Citation
PLoS ONE, Vol.9 No.2, p. e0089122
Abstract
Vanillin is a well-known food and cosmetic additive and has antioxidant and antimutagenic properties. It has also been suggested to have antifungal activity against major human pathogenic fungi, although it is not very effective. In this study, the antifungal activities of vanillin and 33 vanillin derivatives against the human fungal pathogen Cryptococcus neoformans, the main pathogen of cryptococcal meningitis in immunocompromised patients, were investigated. We found a structural correlation between the vanillin derivatives and antifungal activity, showing that the hydroxyl or alkoxy group is more advantageous than the halogenated or nitrated group in benzaldehyde. Among the vanillin derivatives with a hydroxyl or alkoxy group, o-vanillin and o-ethyl vanillin showed the highest antifungal activity against C. neoformans. o-Vanillin was further studied to understand the mechanism of antifungal action. We compared the transcriptome of C. neoformans cells untreated or treated with o-vanillin by using RNA sequencing and found that the compound caused mitochondrial dysfunction and triggered oxidative stress. These antifungal mechanisms of o-vanillin were experimentally confirmed by the significantly reduced growth of the mutants lacking the genes involved in mitochondrial functions and oxidative stress response.
ISSN
1932-6203
URI
https://hdl.handle.net/10371/165768
DOI
https://doi.org/10.1371/journal.pone.0089122
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
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