A Novel Virulence Phenotype Rapidly Assesses Candida Fungal Pathogenesis in Healthy and Immunocompromised Caenorhabditis elegans Hosts
A Novel Virulence Phenotype Rapidly Assesses Candida Fungal Pathogenesis in Healthy and Immunocompromised Caenorhabditis elegans Hosts
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DOI：
10.1128/msphere.00697-18
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发表时间：
2019-03-01
期刊：
影响因子：
4.8
通讯作者：
Hickman, Meleah A.
中科院分区：
文献类型：
--
作者：
Feistel, Dorian J.;Elmostafa, Rema;Hickman, Meleah A.
酵母菌白色念珠菌是人类的机会致病菌，这意味着尽管与其宿主发生细菌相互作用，但它可以转变为有害的病原体。而C.白色念珠菌是在人胃肠道真菌生物群系中分离的主要物种，并且涉及真菌感染，由于非白色念珠菌属物种的感染正在迅速上升。研究影响毒力的因素通常具有挑战性，并且通常取决于许多情况，包括宿主免疫状态和病原体遗传背景。在这里，我们利用线虫秀丽隐杆线虫作为一个清晰和有效的模式宿主系统来研究念珠菌病原体的真菌感染。我们发现，除了减少宿主的生存寿命，暴露于C。白色念珠菌导致繁殖延迟，这显著降低了多代的谱系生长。此外，我们评估了真菌病原体在C.线虫宿主的先天免疫功能受损，并检测到相对于受感染的健康宿主，早期死亡率增加、幼仔大小减少和繁殖延迟。重要的是，通过评估健康和免疫受损宿主背景中的毒力，我们揭示了非白色念珠菌属的病原体潜力。两者合计，我们提出了一种新的谱系生长测定，以衡量减少与真菌感染相关的主机健身和证明病原体和主机的免疫功能，有助于vitrificity.IMPORTANCE之间的显着相互作用病原体是能够引起疾病的病原体，是严重威胁人类健康。了解机会致病菌致病的机制和宿主环境是至关重要的。在这项工作中，我们提出了一种新的方法来快速和定量测量病原体的毒力在健康和免疫功能低下的线虫宿主。我们发现，念珠菌属，人类最突出的真菌条件致病菌之一，通过减少生存和影响宿主繁殖来降低宿主适应性。最重要的是，通过测量具有完整或受损免疫功能的宿主的毒力，我们可以揭示机会性真菌病原体的致病潜力。
The yeast Candida albicans is an opportunistic pathogen of humans, meaning that despite commensal interactions with its host, it can transition to a harmful pathogen. While C. albicans is the predominant species isolated in the human gastrointestinal mycobiome and is implicated in fungal infection, infections due to non-albicans Candida species are rapidly rising. Studying the factors that contribute to virulence is often challenging and frequently depends on many contexts, including host immune status and pathogen genetic background. Here, we utilize the nematode Caenorhabditis elegans as a perspicuous and efficient model host system to study fungal infections of Candida pathogens. We find that, in addition to reducing lifetime host survival, exposure to C. albicans results in delayed reproduction, which significantly reduced lineage growth over multiple generations. Furthermore, we assessed fungal pathogen virulence in C. elegans hosts compromised for innate immune function and detected increased early mortality, reduced brood sizes, and delayed reproduction relative to infected healthy hosts. Importantly, by assessing virulence in both healthy and immunocompromised host backgrounds, we reveal the pathogen potential in non-albicans Candida species. Taken together, we present a novel lineage growth assay to measure reduction in host fitness associated with fungal infection and demonstrate significant interactions between pathogen and host immune function that contribute to virulence.IMPORTANCE Opportunistic pathogens are commensals capable of causing disease and are serious threats to human health. It is critical to understand the mechanisms and host contexts under which opportunistic pathogens become virulent. In this work, we present a novel assay to quickly and quantitatively measure pathogen virulence in healthy and immunocompromised nematode hosts. We found that Candida species, one of the most prominent fungal opportunistic pathogens of humans, decrease host fitness by reducing survival and impacting host reproduction. Most importantly, by measuring virulence in hosts that have intact or compromised immune function, we can reveal the pathogenic potential of opportunistic fungal pathogens.