Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Methods Mol Biol. 2022;2517:299-316. doi: 10.1007/978-1-0716-2417-3_24.
While mammalian models remain the gold standard to study invasive mycoses, mini-host invertebrate models have provided complementary platforms for explorative investigations of fungal pathogenesis, host-pathogen interplay, and antifungal therapy. Specifically, our group has established Toll-deficient Drosophila melanogaster flies as a facile and cost-effective model organism to study candidiasis, and we have recently expanded these studies to the emerging and frequently multidrug-resistant yeast pathogen Candida auris. Our proof-of-concept data suggest that fruit flies could hold a great promise for large-scale applications in antifungal drug discovery and the screening of C. auris (mutant) libraries with disparate pathogenic capacity. This chapter discusses the advantages and limitations of D. melanogaster to study C. auris candidiasis and provides a step-by-step guide for establishing and troubleshooting C. auris infection and antifungal treatment of Toll-deficient flies along with essential downstream readouts.
虽然哺乳动物模型仍然是研究侵袭性真菌感染的金标准,但小型宿主无脊椎动物模型为探索真菌发病机制、宿主-病原体相互作用和抗真菌治疗提供了补充平台。具体来说,我们的小组已经建立了 Toll 缺陷型果蝇 Drosophila melanogaster 作为一种简便且具有成本效益的模式生物来研究念珠菌病,我们最近将这些研究扩展到新兴的、经常具有多重耐药性的酵母病原体 Candida auris。我们的概念验证数据表明,果蝇在大规模应用于抗真菌药物发现和具有不同致病能力的 C. auris(突变体)文库筛选方面具有很大的潜力。本章讨论了使用 D. melanogaster 研究 C. auris 念珠菌病的优点和局限性,并提供了建立和解决 Toll 缺陷型果蝇 C. auris 感染和抗真菌治疗问题的分步指南,以及必要的下游检测方法。