Is It Time To Kill the Survival Curve? A Case for Disease Progression Factors in Microbial Pathogenesis and Host Defense Research.
Is It Time To Kill the Survival Curve? A Case for Disease Progression Factors in Microbial Pathogenesis and Host Defense Research.
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DOI：
10.1128/mbio.03483-20
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发表时间：
2021-02-09
期刊：
影响因子：
6.4
通讯作者：
Kowalski CH
中科院分区：
文献类型：
--
作者：
Cramer RA;Kowalski CH
微生物毒力和宿主防御的分子机制通常是通过动物模型和科赫分子假设来研究的。这些类型的实验的一个共同的基本原理是基于这样的假设来确定治疗靶点，即赋予极端动物模型生存表型的微生物或宿主因素代表关键的毒力和宿主防御因素。微生物毒力和宿主防御的分子机制通常是通过动物模型和科赫分子假设来研究的。这些类型的实验的一个共同的基本原理是基于这样的假设来确定治疗靶点，即赋予极端动物模型生存表型的微生物或宿主因素代表关键的毒力和宿主防御因素。然而，微生物(或宿主)因子的零突变菌株通常会产生极端的生存曲线表型，因为它们无法确定感染。缺乏感染和疾病建立阻碍了对给定因素在疾病进展中的作用的真实评估(S)。在这里，我们假设，在真菌感染疾病模型中，对极端生存曲线表型的强调正导致错过识别新的真菌和宿主因素的机会，这些因素对疾病进展至关重要。我们只是对真菌的毒力和整个感染过程中的宿主防御机制还没有足够的了解。我们认为，有必要开发新的方法，并重新审视已证明有效的方法，以确定超越生存曲线表型分析的感染部位生物学。为了刺激这些新的方法，我们提出了(新的)术语“疾病起始因子”和“疾病进展因子”，以区分感染的不同时间阶段的功能角色，并为我们提供目标，以促进新的发现。
The molecular mechanisms of microbial virulence and host defense are most often studied using animal models and Koch’s molecular postulates. A common rationale for these types of experiments is to identify therapeutic targets based on the assumption that microbial or host factors that confer extreme animal model survival phenotypes represent critical virulence and host defense factors. The molecular mechanisms of microbial virulence and host defense are most often studied using animal models and Koch’s molecular postulates. A common rationale for these types of experiments is to identify therapeutic targets based on the assumption that microbial or host factors that confer extreme animal model survival phenotypes represent critical virulence and host defense factors. Yet null mutant strains of microbial (or host) factors often yield extreme survival curve phenotypes because they fail to establish an infection. The lack of infection and disease establishment prevents true assessment of the given factor’s role(s) in disease progression. Here, we posit that the emphasis on extreme survival curve phenotypes in fungal infectious disease models is leading to missed opportunities to identify new fungal and host factors critical for disease progression. We simply do not yet have a sufficient understanding of fungal virulence and host defense mechanisms throughout the temporal course of an infection. We propose that there is a need to develop new approaches and to revisit tried and true methods to define infection site biology beyond the analysis of survival curve phenotypes. To stimulate these new approaches, we propose the (new) terms “disease initiation factor” and “disease progression factor” to distinguish functional roles at distinct temporal stages of an infection and give us targets to foster new discoveries.