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首页> 外文期刊>Infection and immunity >Isolation and characterization of a pigmentless-conidium mutant of Aspergillus fumigatus with altered conidial surface and reduced virulence.
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Isolation and characterization of a pigmentless-conidium mutant of Aspergillus fumigatus with altered conidial surface and reduced virulence.

机译：具有改变的分生孢子表面和降低的毒力的烟曲霉无色素分生孢子突变体的分离和表征。

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Aspergillus fumigatus is an important pathogen of immunocompromised hosts, causing pneumonia and invasive disseminated disease with high mortality. The factors contributing to the predominance of A. fumigatus as an opportunistic pathogen are largely unknown. Since the survival of conidia in the host is a prerequisite for establishing disease, we have been attempting to identify factors which are associated with conidia and, simultaneously, important for infection. Therefore, an A. fumigatus mutant strain (white [W]) lacking conidial pigmentation was isolated. Scanning electron microscopy revealed that conidia of the W mutant also differed in their surface morphology from those of the wild type (WT). Mutant (W) and WT conidia were compared with respect to their capacities to stimulate an oxidative response in human phagocytes, their intracellular survival in human monocytes, and virulence in a murine animal model. Luminol-dependent chemiluminescence was 10-fold higher when human neutrophils or monocytes were challenged with W conidia compared with WT conidia. Furthermore, mutant conidia were more susceptible to killing by oxidants in vitro and were more efficiently damaged by human monocytes in vitro than WT conidia. In a murine animal model, the W mutant strain showed reduced virulence compared with the WT. A reversion analysis of the W mutant demonstrated that all phenotypes associated with the W mutant, i.e., altered conidial surface, amount of reactive oxygen species release, susceptibility to hydrogen peroxide, and reduced virulence in an murine animal model, coreverted in revertants which had regained the ability to produce green spores. This finding strongly suggests that the A. fumigatus mutant described here carries a single mutation which caused all of the observed phenotypes. Our results suggest that the conidium pigment or a structural feature related to it contributes to fungal resistance against host defense mechanisms in A. fumigatus infections.
机译：烟曲霉是免疫功能低下宿主的重要病原体，导致肺炎和侵入性传播疾病，死亡率很高。导致烟曲霉成为机会病原体优势的因素在很大程度上是未知的。由于分生孢子在宿主中的存活是确定疾病的先决条件，因此我们一直在尝试确定与分生孢子有关并且同时对感染很重要的因素。因此，分离出没有分生孢子色素沉着的烟曲霉突变株（白色[W]）。扫描电子显微镜显示，W突变体的分生孢子的表面形态也与野生型（WT）的分生孢子不同。比较了突变体（W）和WT分生孢子在人吞噬细胞中刺激氧化反应的能力，在人单核细胞中的细胞内存活以及在鼠类动物模型中的毒力。与WT分生孢子相比，W分生孢子攻击人类嗜中性粒细胞或单核细胞时，鲁米诺依赖性化学发光要高出10倍。此外，突变体分生孢子比WT分生孢子更容易在体外被氧化剂杀死，并且在体外更容易被人单核细胞破坏。在鼠类动物模型中，与WT相比，W突变株显示出降低的毒力。对W突变体的回复分析表明，与W突变体相关的所有表型，即改变的分生孢子表面，活性氧的释放量，对过氧化氢的敏感性以及在鼠动物模型中的毒力降低，都已经转化为可恢复的回复体。产生绿色孢子的能力。这一发现有力地表明，这里描述的烟曲霉突变体携带单个突变，该突变导致了所有观察到的表型。我们的结果表明，分生孢子色素或与其有关的结构特征有助于抵抗烟曲霉感染宿主防御机制的真菌。

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