Novel mitochondrial complex I-inhibiting peptides restrain NADH dehydrogenase activity

The emergence of drug-resistant fungal pathogens is becoming increasingly serious due to overuse of antifungals. Antimicrobial peptides have potent activity against a broad spectrum of pathogens, including fungi, and are considered a potential new class of antifungals. In this study, we examined the...

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Bibliographic Details
Published in:Scientific reports 2019-09, Vol.9 (1), p.13694-12, Article 13694
Main Authors: Xue, Yao-Peng, Kao, Mou-Chieh, Lan, Chung-Yu
Format: Article
Language:English
Subjects:
631/326/22/1292
631/61
Antifungal agents
Antifungal Agents - pharmacology
Antimicrobial peptides
Candida albicans
Candida albicans - drug effects
Candida albicans - metabolism
Dehydrogenases
Drug resistance
Electron transport chain
Electron Transport Complex I - antagonists & inhibitors
Fungi
Histatins - pharmacology
Humanities and Social Sciences
Microbial Sensitivity Tests
Mitochondria
Mitochondria - drug effects
Mitochondria - metabolism
multidisciplinary
NADH
NADH dehydrogenase
NADH Dehydrogenase - metabolism
NADH-ubiquinone oxidoreductase
Pathogens
Peptides
Reactive Oxygen Species - metabolism
Science
Science (multidisciplinary)
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Summary:The emergence of drug-resistant fungal pathogens is becoming increasingly serious due to overuse of antifungals. Antimicrobial peptides have potent activity against a broad spectrum of pathogens, including fungi, and are considered a potential new class of antifungals. In this study, we examined the activities of the newly designed peptides P-113Du and P-113Tri, together with their parental peptide P-113, against the human fungal pathogen Candida albicans . The results showed that these peptides inhibit mitochondrial complex I, specifically NADH dehydrogenase, of the electron transport chain. Moreover, P-113Du and P-113Tri also block alternative NADH dehydrogenases. Currently, most inhibitors of the mitochondrial complex I are small molecules or artificially-designed antibodies. Here, we demonstrated novel functions of antimicrobial peptides in inhibiting the mitochondrial complex I of C . albican s, providing insight in the development of new antifungal agents.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-50114-2