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首页> 外文期刊>Infection and immunity >ALL2, a Homologue of ALL1, Has a Distinct Role in Regulating pH Homeostasis in the Pathogen Cryptococcus neoformans
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ALL2, a Homologue of ALL1, Has a Distinct Role in Regulating pH Homeostasis in the Pathogen Cryptococcus neoformans

机译：ALL2，ALL1的同系物，在调节病原性隐球菌的pH稳态中起不同的作用

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Cryptococcus neoformans is a facultative intracellular fungal pathogen that has a polysaccharide capsule and causes life-threatening meningoencephalitis. Its capsule, as well as its ability to survive in the acidic environment of the phagolysosome, contributes to the pathogen's resilience in the host environment. Previously, we reported that downregulation of allergen 1 (ALL1) results in the secretion of a shorter, more viscous exopolysaccharide with less branching and structural complexity, as well as altered iron homeostasis. Now, we report on a homologous coregulated gene, allergen 2 (ALL2). ALL2's function was characterized by generating null mutants in C. neoformans. In contrast to ALL1, loss of ALL2 attenuated virulence in the pulmonary infection model. The all2Δ mutant shed a less viscous exopolysaccharide and exhibited higher sensitivity to hydrogen peroxide than the wild type, and as a result, the all2Δ mutant was more resistant to macrophage-mediated killing. Transcriptome analysis further supported the distinct function of these two genes. Unlike ALL1's involvement in iron homeostasis, we now present data on ALL2's unique function in maintaining intracellular pH in low-pH conditions. Thus, our data highlight that C. neoformans, a human-pathogenic basidiomycete, has evolved a unique set of virulence-associated genes that contributes to its resilience in the human niche.
机译：新型隐球菌是一种兼性的细胞内真菌病原体，具有多糖荚膜并引起危及生命的脑膜脑炎。它的胶囊以及在吞噬酶体的酸性环境中生存的能力有助于病原体在宿主环境中的复原力。以前，我们报道过，过敏原1（ ALL1 ）的下调会导致分泌较短，粘性更大的胞外多糖，且分支和结构复杂性降低，铁稳态也随之改变。现在，我们报道了一个同源的有核基因，过敏原2（ ALL2 ）。 ALL2 的功能通过在新孢梭菌中产生无效突变体来表征。与 ALL1 相比， ALL2 的缺失在肺部感染模型中减弱了毒力。与野生型相比， all2 Δ突变体的黏附性较低，对过氧化氢的敏感性更高，因此， all2 Δ突变体对巨噬细胞的耐药性更高。介导的杀戮。转录组分析进一步支持了这两个基因的独特功能。与 ALL1 参与铁稳态不同，我们现在提供有关 ALL2 在低pH条件下维持细胞内pH的独特功能的数据。因此，我们的数据突出表明，人类致病的担子菌新孢梭菌已进化出一组独特的与毒力相关的基因，有助于其在人类生态位中的适应力。

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