Martinez Melissa, Garsin Danielle A, Lorenz Michael C
Department of Microbiology and Molecular Genetics, University of Texas McGovern Medical School and the University of Texas Graduate School of Biomedical Sciences, USA.
Department of Microbiology and Molecular Genetics, University of Texas McGovern Medical School and the University of Texas Graduate School of Biomedical Sciences, USA.
Curr Opin Microbiol. 2024 Aug;80:102506. doi: 10.1016/j.mib.2024.102506. Epub 2024 Jun 25.
Candida auris is an emerging fungal pathogen with several concerning qualities. First recognized in 2009, it has arisen in multiple geographically distinct genomic clades nearly simultaneously. C. auris strains are typically multidrug resistant and colonize the skin much better than most other pathogenic fungi; it also persists on abiotic surfaces, enabling outbreaks due to transmission in health care facilities. All these suggest a biology substantially different from the 'model' fungal pathogen, Candida albicans and support intensive investigation of C. auris biology directly. To uncover novel virulence mechanisms in this species requires the development of appropriate animal infection models. Various studies using mice, the definitive model, are inconsistent due to differences in mouse and fungal strains, immunosuppressive regimes, doses, and outcome metrics. At the same time, developing models of skin colonization present a route to new insights into an aspect of fungal pathogenesis that has not been well studied in other species. We also discuss the growing use of nonmammalian model systems, including both vertebrates and invertebrates, such as zebrafish, C. elegans, Drosophila, and Galleria mellonella, that have been productively employed in virulence studies with other fungal species. This review will discuss progress in developing appropriate animal models, outline current challenges, and highlight opportunities in demystifying this curious species.
耳念珠菌是一种新出现的具有多种令人担忧特性的真菌病原体。它于2009年首次被发现，几乎同时在多个地理上不同的基因组进化枝中出现。耳念珠菌菌株通常具有多重耐药性，并且比大多数其他致病真菌更易于在皮肤上定殖；它还能在非生物表面存活，导致在医疗机构中传播而引发疫情。所有这些都表明其生物学特性与“典型”真菌病原体白色念珠菌有很大不同，这支持了直接深入研究耳念珠菌生物学特性的必要性。要揭示该物种新的致病机制，需要开发合适的动物感染模型。使用小鼠这一经典模型进行的各种研究结果并不一致，原因在于小鼠和真菌菌株、免疫抑制方案、剂量以及结果指标存在差异。与此同时，开发皮肤定殖模型为深入了解真菌发病机制中一个在其他物种中尚未得到充分研究的方面提供了途径。我们还将讨论非哺乳动物模型系统的日益广泛应用，包括脊椎动物和无脊椎动物，如斑马鱼、秀丽隐杆线虫、果蝇和大蜡螟，这些模型已成功应用于其他真菌物种的毒力研究。这篇综述将讨论开发合适动物模型的进展，概述当前面临的挑战，并突出在揭开这个奇特物种神秘面纱方面的机遇。
