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首页> 外文OA文献 >Chitosan, the Deacetylated Form of Chitin, Is Necessary for Cell Wall Integrity in Cryptococcus neoformans▿ †
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Chitosan, the Deacetylated Form of Chitin, Is Necessary for Cell Wall Integrity in Cryptococcus neoformans▿ †

机译：壳聚糖，几丁质的脱乙酰化形式，对于新隐球菌的细胞壁完整性是必需的。

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Cryptococcus neoformans is an opportunistic fungal pathogen that causes cryptococcal meningoencephalitis, particularly in immunocompromised patients. The fungal cell wall is an excellent target for antifungal therapies as it is an essential organelle that provides cell structure and integrity, it is needed for the localization or attachment of known virulence factors, including the polysaccharide capsule, melanin, and phospholipase, and it is critical for host-pathogen interactions. In C. neoformans, chitosan produced by the enzymatic removal of acetyl groups from nascent chitin polymers has been implicated as an important component of the vegetative cell wall. In this study, we identify four putative chitin/polysaccharide deacetylases in C. neoformans. We have demonstrated that three of these deacetylases, Cda1, Cda2, and Cda3, can account for all of the chitosan produced during vegetative growth in culture, but the function for one, Fpd1, remains undetermined. The data suggest a model for chitosan production in vegetatively growing C. neoformans where the three chitin deacetylases convert chitin generated by the chitin synthase Chs3 into chitosan. Utilizing a collection of chitin/polysaccharide deacetylase deletion strains, we determined that during vegetative growth, chitosan helps to maintain cell integrity and aids in bud separation. Additionally, chitosan is necessary for maintaining normal capsule width and the lack of chitosan results in a “leaky melanin” phenotype. Our analysis indicates that chitin deacetylases and the chitosan made by them may prove to be excellent antifungal targets.
机译：新型隐球菌是一种机会性真菌病原体，可引起隐球菌脑膜脑炎，尤其是在免疫功能低下的患者中。真菌细胞壁是抗真菌治疗的极佳靶标，因为它是提供细胞结构和完整性的重要细胞器，对于定位或附着已知的毒力因子（包括多糖胶囊，黑色素和磷脂酶）是必需的，对于宿主-病原体相互作用至关重要。在新孢梭菌中，通过酶促从新生的几丁质聚合物中去除乙酰基产生的壳聚糖被认为是营养细胞壁的重要组成部分。在这项研究中，我们确定了四个假想的壳聚糖/多糖脱乙酰酶。我们已经证明，这些脱乙酰基酶中的三个Cda1，Cda2和Cda3可以解释在营养生长过程中产生的所有壳聚糖，但是其中一个的功能Fpd1仍然不确定。数据表明在营养生长的新孢子虫中壳聚糖生产的模型，其中三种甲壳质脱乙酰基酶将由甲壳质合酶Chs3生成的甲壳质转化为壳聚糖。利用几丁质/多糖脱乙酰基酶缺失菌株，我们确定在营养生长期间，壳聚糖有助于维持细胞完整性并有助于芽分离。另外，壳聚糖对于维持正常的胶囊宽度是必要的，缺乏壳聚糖会导致“黑色素泄漏”表型。我们的分析表明，几丁质脱乙酰酶和由它们制成的壳聚糖可能被证明是极好的抗真菌靶标。

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