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首页> 外文期刊>Infection and immunity >RNA Interference-Mediated Silencing of the YPS3 Gene of Histoplasma capsulatum Reveals Virulence Defects
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RNA Interference-Mediated Silencing of the YPS3 Gene of Histoplasma capsulatum Reveals Virulence Defects

机译：RNA介导的荚膜胞浆虫YPS3基因沉默显示毒力缺陷。

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The YPS3 gene of Histoplasma capsulatum encodes a protein that is both surface localized in the cell wall of H. capsulatum and released into the culture medium. This protein is produced only during the pathogenic yeast phase of infection and is also expressed differentially in H. capsulatum strains of different virulence levels. In this study, we silenced the YPS3 transcript by using an interfering-RNA strategy and examined the silenced mutants for phenotypic differences in vitro and during infection. The mutants showed no growth defect during in vitro culture in a defined medium at 37°C and appeared to have normal virulence in a RAW 264.7 murine macrophage-like cell line. In a C57BL/6 mouse model of infection, however, the mutants caused significantly decreased fungal burdens, particularly in the peripheral phagocyte-rich tissues of livers and spleens. This defect in organ colonization was evident within 3 days of infection; however, it appeared to be exacerbated at later time points.
机译：荚膜组织胞浆菌的 YPS3 基因编码一种蛋白质，其表面均位于 H的细胞壁中。荚膜并释放到培养基中。该蛋白质仅在感染的致病性酵母菌阶段产生，并在 H中差异表达。不同毒力水平的荚膜菌株。在这项研究中，我们通过使用干扰RNA策略沉默了 YPS3 转录本，并检查了沉默突变体在体外和感染期间的表型差异。在37°C的特定培养基中进行体外培养时，这些突变体没有生长缺陷，并且在RAW 264.7鼠巨噬细胞样细胞系中似乎具有正常的毒力。然而，在感染的C57BL / 6小鼠模型中，突变体引起真菌负担明显减少，尤其是在肝脏和脾脏的富于吞噬细胞的外周组织中。感染后三天内，这种器官定植的缺陷很明显。但是，它似乎在以后的时间点恶化了。

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