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首页> 外文期刊>Infection and immunity >Redundant Catalases Detoxify Phagocyte Reactive Oxygen and Facilitate Histoplasma capsulatum Pathogenesis
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Redundant Catalases Detoxify Phagocyte Reactive Oxygen and Facilitate Histoplasma capsulatum Pathogenesis

机译：多余的过氧化氢酶解毒吞噬细胞的活性氧并促进组织胞浆囊病的发病机理

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Histoplasma capsulatum is a respiratory pathogen that infects phagocytic cells. The mechanisms allowing Histoplasma to overcome toxic reactive oxygen molecules produced by the innate immune system are an integral part of Histoplasma's ability to survive during infection. To probe the contribution of Histoplasma catalases in oxidative stress defense, we created and analyzed the virulence defects of mutants lacking CatB and CatP, which are responsible for extracellular and intracellular catalase activities, respectively. Both CatB and CatP protected Histoplasma from peroxide challenge in vitro and from antimicrobial reactive oxygen produced by human neutrophils and activated macrophages. Optimal protection required both catalases, as the survival of a double mutant lacking both CatB and CatP was lower than that of single-catalase-deficient cells. Although CatB contributed to reactive oxygen species defenses in vitro, CatB was dispensable for lung infection and extrapulmonary dissemination in vivo. Loss of CatB from a strain also lacking superoxide dismutase (Sod3) did not further reduce the survival of Histoplasma yeasts. Nevertheless, some catalase function was required for pathogenesis since simultaneous loss of both CatB and CatP attenuated Histoplasma virulence in vivo. These results demonstrate that Histoplasma's dual catalases comprise a system that enables Histoplasma to efficiently overcome the reactive oxygen produced by the innate immune system.
机译：荚膜组织胞浆菌是一种感染吞噬细胞的呼吸道病原体。允许组织胞浆克服先天免疫系统产生的有毒活性氧分子的机制，是组织胞浆在感染过程中生存能力不可或缺的一部分。为了探究组织胞质过氧化氢酶在氧化应激防御中的作用，我们创建并分析了缺少CatB和CatP突变体的突变体的毒力缺陷，这两个突变体分别负责细胞外和细胞内过氧化氢酶的活性。 CatB和CatP都可以保护组织胞浆免受体外过氧化物的攻击以及人类嗜中性粒细胞和活化巨噬细胞产生的抗菌活性氧。最佳保护需要两个催化作用，因为同时缺乏CatB和CatP的双突变体的存活率比缺乏单一过氧化氢酶的细胞的存活率低。尽管CatB在体外有助于活性氧的防御，但CatB对于体内的肺部感染和肺外传播是不可缺少的。从同样缺乏超氧化物歧化酶（Sod3）的菌株中丢失CatB并没有进一步降低组织胞浆酵母的存活率。然而，由于CatB和CatP的同时丧失会减弱体内的组织胞浆毒力，因此发病机理需要某些过氧化氢酶功能。这些结果表明，组织胞浆菌的双重过氧化氢酶组成了一个系统，该系统可使组织胞浆菌有效地克服先天免疫系统产生的活性氧。

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