A dissemination-prone morphotype enhances extrapulmonary organ entry by Cryptococcus neoformans.

A dissemination-prone morphotype enhances extrapulmonary organ entry by Cryptococcus neoformans.
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DOI:
10.1016/j.chom.2022.08.017
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发表时间:
2022-10-12
影响因子:
30.3
通讯作者:
Brown, Jessica C. S.
Brown, Jessica C. S.
中科院分区:
医学1区
文献类型:
--
作者:
Denham, Steven T.;Brammer, Brianna;Chung, Krystal Y.;Wambaugh, Morgan A.;Bednarek, Joseph M.;Guo, Li;Moreau, Christian T.;Brown, Jessica C. S.

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环境病原体从生态位转移到哺乳动物宿主,需要适应截然不同的环境。传播更远的微生物,包括脑膜炎真菌病原体新型隐球菌,需要额外适应不同的组织。我们证明了小的新生芽胞杆菌形态的形成——由于其定植能力而被称为“种子”细胞——对于肺外器官的进入至关重要。种子细胞表现出真菌细胞大小和表面表达的变化,导致巨噬细胞更新增强。种子细胞的形成受环境因素的影响,其中新生物的环境生态位、含磷酸盐的鸽子鸟粪起主要作用。种子细胞的磷酸盐获取基因表达增强,不能获得磷酸盐的突变体不能采用种子细胞形态。此外,磷酸盐可以通过组织损伤释放,潜在地建立种子细胞形成和播散的前馈循环。因此,新形态芽孢杆菌的大小变化代表了可诱导的形态,它改变了宿主的相互作用,从而促进了微生物的传播。在感染过程中传播的环境微生物必须适应不同的环境。Denham等人发现了一种诱导型,可促进致病性新型隐球菌进入器官。磷酸盐浓度的改变诱导了这种小形态,促进了真菌从肺部退出并传播到其他器官。
Environmental pathogens move from ecological niches to mammalian hosts, requiring adaptation to dramatically different environments. Microbes that disseminate farther, including the fungal meningitis pathogen Cryptococcus neoformans, require additional adaptation to diverse tissues. We demonstrate that formation of a small C. neoformans morphotype – called “seed” cells due to their colonizing ability – is critical for extrapulmonary organ entry. Seed cells exhibit changes in fungal cell size and surface expression that result in enhanced macrophage update. Seed cell formation is triggered by environmental factors, including C. neoformans’ environmental niche, pigeon guano with phosphate playing central roles. Seed cells show enhanced expression of phosphate acquisition genes and mutants unable to acquire phosphate fail to adopt the seed cell morphotype. Additionally, phosphate can be released by tissue damage, potentially establishing a feed-forward loop of seed cell formation and dissemination. Thus, C. neoformans’ size variation represent inducible morphotypes that change host interactions to facilitate microbe spread. Environmental microbes that disseminate during infection must adjust to disparate environments. Denham et al. identifies an inducible morphotype that facilitates organ entry by the pathogenic fungus Cryptococcus neoformans. Alterations in phosphate concentration induce this small morphotype, facilitating fungal exit from the lung and dissemination to other organs.
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