Department of Biology, Emory University, Atlanta, Georgia, USA.
Department of Biology, Emory University, Atlanta, Georgia, USA
mSphere. 2019 Apr 10;4(2):e00697-18. doi: 10.1128/mSphere.00697-18.
The yeast is an opportunistic pathogen of humans, meaning that despite commensal interactions with its host, it can transition to a harmful pathogen. While is the predominant species isolated in the human gastrointestinal mycobiome and is implicated in fungal infection, infections due to non-albicans 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 as a perspicuous and efficient model host system to study fungal infections of pathogens. We find that, in addition to reducing lifetime host survival, exposure to results in delayed reproduction, which significantly reduced lineage growth over multiple generations. Furthermore, we assessed fungal pathogen virulence in 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 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. 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 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.
酵母是人类机会性病原体，这意味着尽管与宿主存在共生关系，但它可以转变为有害病原体。虽然 是人类胃肠道真菌组中分离出的主要物种，并与真菌感染有关，但由于非白念珠菌 物种引起的感染正在迅速增加。研究导致毒力的因素通常具有挑战性，并且常常取决于许多因素，包括宿主免疫状态和病原体遗传背景。在这里，我们利用线虫作为一种清晰而有效的模式宿主系统来研究真菌对 病原体的感染。我们发现，除了降低宿主的寿命外，暴露于 还会导致繁殖延迟，这会显著降低多个世代的谱系生长。此外，我们评估了先天免疫功能受损的 宿主中的真菌病原体毒力，并发现与感染健康宿主相比，早期死亡率增加、后代数量减少和繁殖延迟。重要的是，通过在健康和免疫功能受损的宿主背景下评估毒力，我们揭示了非白念珠菌 物种的病原体潜力。总之，我们提出了一种新的谱系生长测定法来衡量与真菌感染相关的宿主适应性降低，并证明了病原体与宿主免疫功能之间的相互作用对毒力有重要影响。机会性病原体是能够引起疾病的共生体，对人类健康构成严重威胁。了解机会性病原体变得有毒的机制和宿主背景至关重要。在这项工作中，我们提出了一种新的测定法，用于快速定量测量健康和免疫功能受损线虫宿主中的病原体毒力。我们发现，人类最主要的真菌机会性病原体之一 物种通过降低宿主存活率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中的毒力，我们可以揭示机会性病原体的致病潜力。
