Long-chain 4-aminoquinolines inhibit filamentation and increase efficacy of nystatin against Candida albicans infections in vivo

Autor: Aleksandar Pavic, Natasa Radakovic, Ivana Moric, Nada Stankovic, Dejan Opsenica, Lidija Senerovic
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: npj Biofilms and Microbiomes, Vol 10, Iss 1, Pp 1-11 (2024)
Druh dokumentu: article
ISSN: 2055-5008
DOI: 10.1038/s41522-024-00608-3
Popis: Abstract In exploring a growing demand for innovative approaches to tackle emerging and life threatening fungal diseases, we identified long-chain 4-aminoquinoline (4-AQ) derivatives as a new class of anti-virulence agents. For the first time, we demonstrated that 4-AQs effectively prevent filamentation of Candida albicans, a key virulence trait, under multiple triggering conditions. Selected 4-AQ derivatives inhibited filament formation in a zebrafish model of disseminated candidiasis at 1.56 µM, with no toxicity up to 50 µM. Combining nystatin with 4-AQs resulted in a 100% survival rate of infected embryos and complete eradication of C. albicans, compared to 65–75% survival with nystatin alone. The most potent 4-AQ derivatives also showed significant activity against C. albicans biofilms, with derivative 11 suppressing mixed C. albicans-Pseudomonas aeruginosa biofilms. This dual capability highlights the potential of 4-AQs as novel anti-virulence agents to enhance conventional antifungal therapies, marking a significant advance in treating complex fungal infections.
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