Hazen K C, Wu J G, Masuoka J
Department of Pathology, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Infect Immun. 2001 Feb;69(2):779-86. doi: 10.1128/IAI.69.2.779-786.2001.
Although Candida dubliniensis is a close genetic relative of Candida albicans, it colonizes and infects fewer sites. Nearly all instances of candidiasis caused by C. dubliniensis are restricted to the oral cavity. As cell surface hydrophobicity (CSH) influences virulence of C. albicans, CSH properties of C. dubliniensis were investigated and compared to C. albicans. Growth temperature is one factor which affects the CSH status of stationary-phase C. albicans. However, C. dubliniensis, similar to other pathogenic non-albicans species of Candida, was hydrophobic regardless of growth temperature. For all Candida species tested in this study (C. albicans, C. dubliniensis, C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis), CSH status correlated with coaggregation with the anaerobic oral bacterium Fusobacterium nucleatum. Previous studies have shown that CSH status of C. albicans involves multiple surface proteins and surface protein N-glycans. The hydrophobic surface glycoprotein CAgp38 appears to be expressed by C. albicans constitutively regardless of growth temperature and medium. C. dubliniensis expresses a 38-kDa protein that cross-reacts with the anti-CAgp38 monoclonal antibody; however, expression of the protein was growth medium and growth temperature dependent. The anti-CAgp38 monoclonal antibody has been shown to inhibit adhesion of C. albicans to extracellular matrix proteins and to vascular endothelial cells. Since protein glycosylation influences the CSH status of C. albicans, we compared the cell wall mannoprotein content and composition between C. albicans and C. dubliniensis. Similar bulk compositional levels of hexose, phosphate, and protein in their N-glycans were determined. However, a component of the C. albicans N-glycan, acid-labile phosphooligomannoside, is expressed much less or negligibly by C. dubliniensis, and when present, the oligomannosides are predominantly less than five mannose residues in length. In addition, the acid-labile phosphooligomannoside profiles varied among the three strains of C. dubliniensis we tested, indicating the N-glycan of C. dubliniensis differs from C. albicans. For C. albicans, the acid-labile phosphooligomannoside influences virulence and surface fibrillar conformation, which affects exposure of hydrophobic surface proteins. Given the combined role in C. albicans of expression of specific surface hydrophobic proteins in pathogenesis and of surface protein glycosylation on exposure of the proteins, the lack of these virulence-associated CSH entities in C. dubliniensis could contribute to its limited ability to cause disseminated infections.
尽管都柏林念珠菌是白色念珠菌的近亲,但它在较少的部位定殖和感染。几乎所有由都柏林念珠菌引起的念珠菌病都局限于口腔。由于细胞表面疏水性(CSH)影响白色念珠菌的毒力,因此对都柏林念珠菌的CSH特性进行了研究,并与白色念珠菌进行了比较。生长温度是影响静止期白色念珠菌CSH状态的一个因素。然而,都柏林念珠菌与念珠菌属其他致病性非白色念珠菌物种相似,无论生长温度如何,都具有疏水性。在本研究中测试的所有念珠菌物种(白色念珠菌、都柏林念珠菌、光滑念珠菌、克鲁斯念珠菌、近平滑念珠菌和热带念珠菌)中,CSH状态与与厌氧口腔细菌具核梭杆菌的共聚集相关。先前的研究表明,白色念珠菌的CSH状态涉及多种表面蛋白和表面蛋白N-聚糖。疏水性表面糖蛋白CAgp38似乎由白色念珠菌组成性表达,无论生长温度和培养基如何。都柏林念珠菌表达一种与抗CAgp38单克隆抗体发生交叉反应的38 kDa蛋白;然而,该蛋白的表达取决于生长培养基和生长温度。抗CAgp38单克隆抗体已被证明可抑制白色念珠菌与细胞外基质蛋白和血管内皮细胞的粘附。由于蛋白质糖基化影响白色念珠菌的CSH状态,我们比较了白色念珠菌和都柏林念珠菌细胞壁甘露糖蛋白的含量和组成。测定了它们N-聚糖中己糖、磷酸盐和蛋白质的类似总体组成水平。然而,白色念珠菌N-聚糖的一种成分,酸不稳定磷酸寡甘露糖苷,在都柏林念珠菌中的表达要少得多或可忽略不计,并且当存在时,寡甘露糖苷的长度主要小于五个甘露糖残基。此外,我们测试的三株都柏林念珠菌的酸不稳定磷酸寡甘露糖苷谱各不相同,表明都柏林念珠菌的N-聚糖与白色念珠菌不同。对于白色念珠菌,酸不稳定磷酸寡甘露糖苷影响毒力和表面纤维状构象,从而影响疏水性表面蛋白的暴露。鉴于特定表面疏水蛋白的表达在白色念珠菌发病机制中的综合作用以及表面蛋白糖基化对这些蛋白暴露的作用,都柏林念珠菌中缺乏这些与毒力相关CSH实体可能导致其引起播散性感染的能力有限。