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利用黄粉虫作为异源宿主研究镰刀菌的发病机制。

Fusarium pathogenesis investigated using Galleria mellonella as a heterologous host.

机构信息

Harvard Medical School, Massachusetts General Hospital, Division of Infectious Diseases, Boston, MA 02114, USA.

出版信息

Fungal Biol. 2011 Dec;115(12):1279-89. doi: 10.1016/j.funbio.2011.09.005. Epub 2011 Oct 4.

Abstract

Members of the fungal genus Fusarium are capable of manifesting in a multitude of clinical infections, most commonly in immunocompromised patients. In order to better understand the interaction between the fungus and host, we have developed the larvae of the greater wax moth, Galleria mellonella, as a heterologous host for fusaria. When conidia are injected into the haemocoel of this Lepidopteran system, both clinical and environmental isolates of the fungus are able to kill the larvae at 37 °C, although killing occurs more rapidly when incubated at 30 °C. This killing was dependent on several other factors besides temperature, including the Fusarium strain, the number of conidia injected, and the conidia morphology, where macroconidia are more virulent than their microconidia counterpart. There was a correlation in the killing rate of Fusarium spp. when evaluated in G. mellonella and a murine model. In vivo studies indicated G. mellonella haemocytes were capable of initially phagocytosing both conidial morphologies. The G. mellonella system was also used to evaluate antifungal agents, and amphotericin B was able to confer a significant increase in survival to Fusarium-infected larvae. The G. mellonella-Fusarium pathogenicity system revealed that virulence of Fusarium spp. is similar, regardless of the origin of the isolate, and that mammalian endothermy is a major deterrent for Fusarium infection and therefore provides a suitable alternative to mammalian models to investigate the interaction between the host and this increasingly important fungal pathogen.

摘要

镰刀菌属真菌的成员能够表现出多种临床感染,最常见于免疫功能低下的患者。为了更好地理解真菌与宿主之间的相互作用,我们已经开发出了大蜡螟幼虫作为一种异源宿主来研究镰刀菌。当将分生孢子注入这种鳞翅目系统的血腔中时,临床和环境分离株的真菌都能够在 37°C 下杀死幼虫,尽管在 30°C 下孵育时,杀死速度更快。这种杀伤除了温度之外,还依赖于其他几个因素,包括镰刀菌菌株、注射的分生孢子数量和分生孢子形态,其中大分生孢子比小分生孢子更具毒性。在大蜡螟和鼠模型中评估时,发现镰刀菌属的杀伤率存在相关性。体内研究表明,大蜡螟血细胞最初能够吞噬两种形态的分生孢子。大蜡螟系统也被用于评估抗真菌药物,两性霉素 B 能够显著提高感染镰刀菌的幼虫的存活率。大蜡螟-镰刀菌致病性系统表明,镰刀菌属的毒力相似,无论分离株的来源如何,哺乳动物的体温都是抑制镰刀菌感染的主要因素,因此为研究宿主与这种日益重要的真菌病原体之间的相互作用提供了一种替代哺乳动物模型的合适选择。

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