Histoplasma and Paracoccidioides 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, Histoplasma and Paracoccidioides 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.

组织胞浆 和 副球菌与热双态性真菌病原体相关，它们主要在北美，中美洲和南美引起致命的霉菌病（分别是组织胞浆菌病和副球菌病）。哺乳动物感染是由于吸入分生孢子并将其随后转化为致病酵母而引起的。肺中的巨噬细胞是第一道防线，但通常无法清除这些真菌。代替，组织胞浆 和 副球菌酵母在宿主巨噬细胞的吞噬区室中存活并增殖。巨噬细胞内的生长需要从贫营养的吞噬体环境中获取足够的营养（例如，碳，氮以及必需的微量元素和辅助因子）的策略。我们回顾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将其代谢调节为巨噬细胞吞噬体中可用的资源。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后发生变化。了解这些双态病原体在宿主细胞中壮成长时的代谢需求，可以为治疗干预提供新的靶点。