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首页> 外文期刊>Infection and immunity >A 32-Kilodalton Hydrolase Plays an Important Role in Paracoccidioides brasiliensis Adherence to Host Cells and Influences Pathogenicity
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A 32-Kilodalton Hydrolase Plays an Important Role in Paracoccidioides brasiliensis Adherence to Host Cells and Influences Pathogenicity

机译：32 Kilodalton水解酶在巴西副球菌对宿主细胞的粘附中起重要作用，并影响致病性

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摘要

One of the most crucial events during infection with the dimorphic fungus Paracoccidioides brasiliensis is adhesion to pulmonary epithelial cells, a pivotal step in the establishment of disease. In this study, we have evaluated the relevance of a 32-kDa protein, a putative adhesion member of the haloacid dehalogenase (HAD) superfamily of hydrolases, in the virulence of this fungus. Protein sequence analyses have supported the inclusion of PbHad32p as a hydrolase and have revealed a conserved protein only among fungal dimorphic and filamentous pathogens that are closely phylogenetically related. To evaluate its role during the host-pathogen interaction, we have generated mitotically stable P. brasiliensis HAD32 (PbHAD32) antisense RNA (aRNA) strains with consistently reduced gene expression. Knockdown of PbHAD32 did not alter cell vitality or viability but induced morphological alterations in yeast cells. Moreover, yeast cells with reduced PbHAD32 expression were significantly affected in their capacity to adhere to human epithelial cells and presented decreased virulence in a mouse model of infection. These data support the hypothesis that PbHad32p binds to extracellular matrix (ECM) proteins and modulates the initial immune response for evasion of host defenses. Our findings point to PbHAD32 as a novel virulence factor active during the initial interaction with host cells in P. brasiliensis.
机译：在感染双态真菌巴西副球菌的过程中，最关键的事件之一是粘附到肺上皮细胞，这是疾病建立的关键步骤。在这项研究中，我们评估了32 kDa蛋白（一种水解酶的卤酸脱卤酶（HAD）超家族的假定粘附成员）在这种真菌的毒性中的相关性。蛋白质序列分析已支持将PbHad32p包含为水解酶，并且揭示了仅在亲缘关系密切的真菌双态和丝状病原体中存在保守蛋白。若要评估其在宿主-病原体相互作用中的作用，我们已经产生了有丝分裂稳定的巴西假单胞菌HAD32（PbHAD32）反义RNA（aRNA）菌株，其基因表达持续降低。击倒PbHAD32不会改变细胞活力或活力，但会诱导酵母细胞发生形态变化。此外，具有降低的PbHAD32表达的酵母细胞粘附于人上皮细胞的能力受到显着影响，并且在感染的小鼠模型中呈现出降低的毒力。这些数据支持PbHad32p与细胞外基质（ECM）蛋白结合并调节初始免疫反应以逃避宿主防御的假说。我们的研究结果指出，PbHAD32作为一种新型毒力因子，在与巴西假单胞菌宿主细胞的初始相互作用中具有活性。

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