Dunn Matthew J, Woodruff Andrew L, Anderson Matthew Z
Department of Microbiology, The Ohio State University.
Department of Microbiology, The Ohio State University; Department of Microbial Infection and Immunity, The Ohio State University;
J Vis Exp. 2018 Nov 17(141). doi: 10.3791/58914.
Candida species are common fungal commensals of humans colonizing the skin, mucosal surfaces, and gastrointestinal tract. Under certain conditions, Candida can overgrow their natural niches resulting in debilitating mucosal infections as well as life-threatening systemic infections, which are a major focus of investigation due to their associated high mortality rates. Animal models of disseminated infection exist for studying disease progression and dissecting the characteristics of Candida pathogenicity. Of these, the Galleria mellonella waxworm infection model provides a cost-effective experimental tool for high-throughput investigations of systemic virulence. Many other bacterial and eukaryotic infectious agents have been effectively studied in G. mellonella to understand pathogenicity, making it a widely accepted model system. Yet, variation in the method used to infect G. mellonella can alter phenotypic outcomes and complicate interpretation of the results. Here, we outline the benefits and drawbacks of the waxworm model to study systemic Candida pathogenesis and detail an approach to improve reproducibility. Our results highlight the range of mortality kinetics in G. mellonella and describe the variables which can modulate these kinetics. Ultimately, this method stands as an ethical, rapid, and cost-effective approach to study virulence in a model of disseminated candidiasis.
念珠菌属是人类常见的真菌共生菌,定殖于皮肤、粘膜表面和胃肠道。在某些情况下,念珠菌可在其自然生态位过度生长,导致使人虚弱的粘膜感染以及危及生命的全身感染,由于其相关的高死亡率,这些感染是主要的研究重点。存在用于研究疾病进展和剖析念珠菌致病性特征的播散性感染动物模型。其中,大蜡螟感染模型为系统性毒力的高通量研究提供了一种经济高效的实验工具。许多其他细菌和真核感染因子已在大蜡螟中得到有效研究以了解致病性,使其成为一个被广泛接受的模型系统。然而,用于感染大蜡螟的方法的差异可改变表型结果并使结果的解释复杂化。在这里,我们概述了蜡虫模型在研究系统性念珠菌发病机制方面的优缺点,并详细介绍了一种提高可重复性的方法。我们的结果突出了大蜡螟中的死亡动力学范围,并描述了可调节这些动力学的变量。最终,该方法是一种在播散性念珠菌病模型中研究毒力的符合伦理、快速且经济高效的方法。