The Histoplasma capsulatum vacuolar ATPase is required for iron homeostasis, intracellular replication in macrophages and virulence in a murine model of histoplasmosis.
The Histoplasma capsulatum vacuolar ATPase is required for iron homeostasis, intracellular replication in macrophages and virulence in a murine model of histoplasmosis.
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DOI：
10.1111/j.1365-2958.2008.06395.x
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发表时间：
2008-10
影响因子：
3.6
通讯作者：
Newman, Simon L.
中科院分区：
文献类型：
--
作者：
Hilty, Jeremy;Smulian, A. George;Newman, Simon L.
荚膜组织胞浆菌（Histoplasma capsulatum）是一种在巨噬细胞内存活和复制的二型真菌病原体。为了鉴定细胞内存活所需的特定基因，我们利用根癌农杆菌介导的诱变，并筛选H。capsulatum插入突变体不能在人M.鉴定出一个菌落在VMA 1（液泡ATP酶（V-ATP酶）的催化亚基A）内插入。vma 1突变株（vma 1：：HPH）在铁营养丰富的培养基上生长正常，而在缺铁的培养基上不能正常生长。在缺铁培养基上，vma 1突变体的生长在野生型（WT）H存在下恢复。capsulatum酵母，或异羟肟酸铁载体，红曲霉酸。然而，无法复制的M-10内，只有部分恢复了外源性铁的加入。vma 1：：HPH突变体在28°C下也不作为霉菌生长。突变体（vma/VMA 1）的互补恢复了其在M β中复制、在缺铁培养基上生长以及在28°C下作为霉菌生长的能力。Vma 1：：HPH突变体在组织胞浆菌病的小鼠模型中是无毒的，而Vma 1/VMA 1菌株与WT酵母一样具有致病性。这些研究表明V-ATPase功能在H. capsulatum，铁稳态，和真菌二型性。
Histoplasma capsulatum is a dimorphic fungal pathogen that survives and replicates within macrophages (Mϕ). To identify specific genes required for intracellular survival, we utilized Agrobacterium tumefaciens-mediated mutagenesis, and screened for H. capsulatum insertional mutants that were unable to survive in human Mϕ. One colony was identified that had an insertion within VMA1, the catalytic subunit A of the vacuolar ATPase (V-ATPase). The vma1 mutant (vma1::HPH) grew normally on iron replete medium, but not on iron deficient media. On iron deficient medium, the growth of the vma1 mutant was restored in the presence of wild type (WT) H. capsulatum yeasts, or the hydroxamate siderophore, rhodotorulic acid. However, the inability to replicate within Mϕ was only partially restored by the addition of exogenous iron. The vma1::HPH mutant also did not grow as a mold at 28°C. Complementation of the mutant (vma/VMA1) restored its ability to replicate in Mϕ, grow on iron poor medium, and grow as a mold at 28°C. The vma1::HPH mutant was avirulent in a mouse model of histoplasmosis, whereas the vma1/VMA1 strain was as pathogenic as WT yeasts. These studies demonstrate the importance of V-ATPase function in the pathogenicity of H. capsulatum, in iron homeostasis, and in fungal dimorphism.
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影响因子：
12.3
作者：
Eide DJ;Clark S;Nair TM;Gehl M;Gribskov M;Guerinot ML;Harper JF
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