卡斯波芬金
白色念珠菌
棘白菌素
系统性念珠菌病
白色体
体内
胃肠道
微生物学
真菌病原
病菌
抗真菌药
生物
氟康唑
伏立康唑
抗真菌
生物化学
生物技术
作者
Tim Kaden,Raquel Alonso-Román,Parastoo Akbarimoghaddam,Alexander S. Mosig,Katja Graf,Martin Raasch,Birgit Hoffmann,Marc Thilo Figge,Bernhard Hube,Mark S. Gresnigt
出处
期刊:Biomaterials
[Elsevier]
日期:2024-03-01
卷期号:: 122525-122525
标识
DOI:10.1016/j.biomaterials.2024.122525
摘要
Candida albicans is a commensal yeast of the human intestinal microbiota that, under predisposing conditions, can become pathogenic and cause life-threatening systemic infections (candidiasis). Fungal-host interactions during candidiasis are commonly studied using conventional 2D in vitro models, which have provided critical insights into the pathogenicity. However, microphysiological models with a higher biological complexity may be more suitable to mimic in vivo-like infection processes and antifungal drug efficacy. Therefore, a 3D intestine-on-chip model was used to investigate fungal-host interactions during the onset of invasive candidiasis and evaluate antifungal treatment under clinically relevant conditions. By combining microbiological and image-based analyses we quantified infection processes such as invasiveness and fungal translocation across the epithelial barrier. Additionally, we obtained novel insights into fungal microcolony morphology and association with the tissue. Our results demonstrate that C. albicans microcolonies induce injury to the epithelial tissue by disrupting apical cell-cell contacts and causing inflammation. Caspofungin treatment effectively reduced the fungal biomass and induced substantial alterations in microcolony morphology during infection with a wild-type strain. However, caspofungin showed limited effects after infection with an echinocandin-resistant clinical isolate. Collectively, this organ-on-chip model can be leveraged for in-depth characterization of pathogen-host interactions and alterations due to antimicrobial treatment.
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