PDF(Sci-hub)
Abstract：
The two leading yeast pathogens of humans, Candida albicans and Cryptococcus neoformans, cause systemic infections in >1.4 million patients worldwide with mortality rates approaching 75%. It is thus imperative to study fungal virulence mechanisms, efficacy of antifungal drugs, and host response pathways. While this is commonly done in mammalian models, which are afflicted by ethical and practical concerns, invertebrate models, such as wax moth larvae and nematodes have been introduced over the last two decades. To complement existing invertebrate host models, we developed fifth instar caterpillars of the Tobacco Hornworm moth Manduca sexta as a novel host model. These caterpillars can be maintained at 37°C, are suitable for injections with defined amounts of yeast cells, and are susceptible to the most threatening yeast pathogens, including C. albicans, C. neoformans, C. auris, and C. glabrata. Importantly, fungal burden can be assessed daily throughout the course of infection in a single caterpillar\'s feces and hemolymph. Infected caterpillars can be rescued by treatment with antifungal drugs. Notably, these animals are large enough for weight to provide a reliable and reproducible measure of fungal disease and to facilitate host tissue-specific expression analyses. M. sexta caterpillars combine a suite of parameters that make them suitable for the study of fungal virulence.
摘要：
人类的两种主要酵母病原体，白色念珠菌和新生隐球菌，在全球超过140万患者中引起全身感染,死亡率接近75%.因此，研究真菌毒力机制势在必行，抗真菌药物的功效，和宿主反应途径。虽然这通常在哺乳动物模型中完成，受到道德和实际问题的困扰，无脊椎动物模型，例如蜡蛾幼虫和线虫在过去的二十年中被引入。为了补充现有的无脊椎动物寄主模型，我们开发了烟草角虫蛾Manducasexta的第五龄毛虫作为一种新颖的寄主模型。这些毛毛虫可以保持在37°C，适合注射一定量的酵母细胞，并且易受最具威胁性的酵母病原体的影响，包括白色念珠菌,C.新生主义者，C.auris,和C.glabrata.重要的是,在单个毛虫的粪便和血淋巴的整个感染过程中，可以每天评估真菌负荷。感染的毛虫可以通过抗真菌药物治疗来挽救。值得注意的是,这些动物足够大,体重足以提供可靠和可重复的真菌病测量,并有助于宿主组织特异性表达分析.M.sexta毛虫结合了一套参数，使它们适合于真菌毒力的研究。
