Department of Biology, Rhodes College, Memphis, TN, United States.
Department of Microbiology, Ohio State University, Columbus, OH, United States.
Front Cell Infect Microbiol. 2020 Oct 16;10:592259. doi: 10.3389/fcimb.2020.592259. eCollection 2020.
and are related thermally dimorphic fungal pathogens that cause deadly mycoses (i.e., histoplasmosis and paracoccidioidomycosis, respectively) primarily in North, Central, and South America. Mammalian infection results from inhalation of conidia and their subsequent conversion into pathogenic yeasts. Macrophages in the lung are the first line of defense, but are generally unable to clear these fungi. Instead, and yeasts survive and proliferate within the phagosomal compartment of host macrophages. Growth within macrophages requires strategies for acquisition of sufficient nutrients (e.g., carbon, nitrogen, and essential trace elements and co-factors) from the nutrient-depleted phagosomal environment. We review the transcriptomic and recent functional genetic studies that are defining how these intracellular fungal pathogens tune their metabolism to the resources available in the macrophage phagosome. In addition, recent studies have shown that the nutritional state of the macrophage phagosome is not static, but changes upon activation of adaptive immune responses. Understanding the metabolic requirements of these dimorphic pathogens as they thrive within host cells can provide novel targets for therapeutic intervention.
和 是相关的热二相真菌病原体，主要在北美、中美和南美引起致命的真菌病（即组织胞浆菌病和副球孢子菌病）。哺乳动物感染是由分生孢子的吸入及其随后转化为致病性酵母引起的。肺部的巨噬细胞是第一道防线，但通常无法清除这些真菌。相反， 和酵母在宿主巨噬细胞的吞噬体隔室中存活和增殖。在巨噬细胞内生长需要从营养匮乏的吞噬体环境中获取足够营养（例如碳、氮以及必需的痕量元素和辅助因子）的策略。我们综述了转录组学和最近的功能遗传研究，这些研究定义了这些细胞内真菌病原体如何根据巨噬细胞吞噬体中可用的资源来调节其代谢。此外，最近的研究表明，巨噬细胞吞噬体的营养状态不是静态的，而是在适应性免疫反应激活时发生变化。了解这些二相病原体在宿主细胞内茁壮成长的代谢需求，可以为治疗干预提供新的靶点。
