PUBLICATION
Long-chain 4-aminoquinolines inhibit filamentation and increase efficacy of nystatin against Candida albicans infections in vivo
- Authors
- Pavic, A., Radakovic, N., Moric, I., Stankovic, N., Opsenica, D., Senerovic, L.
- ID
- ZDB-PUB-241214-18
- Date
- 2024
- Source
- NPJ biofilms and microbiomes 10: 146146 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Virulence/drug effects
- Aminoquinolines*/pharmacology
- Antifungal Agents*/pharmacology
- Pseudomonas aeruginosa/drug effects
- Drug Synergism
- Candidiasis*/drug therapy
- Candidiasis*/microbiology
- Candida albicans*/drug effects
- Nystatin*/pharmacology
- Disease Models, Animal*
- Animals
- Microbial Sensitivity Tests
- Biofilms*/drug effects
- Zebrafish*
- PubMed
- 39672811 Full text @ NPJ Biofilms Microbiomes
Citation
Pavic, A., Radakovic, N., Moric, I., Stankovic, N., Opsenica, D., Senerovic, L. (2024) Long-chain 4-aminoquinolines inhibit filamentation and increase efficacy of nystatin against Candida albicans infections in vivo. NPJ biofilms and microbiomes. 10:146146.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping