Alvarado María, Gómez-Navajas Jesús A, Blázquez-Muñoz María Teresa, Gómez-Molero Emilia, Fernández-Sánchez Sebastián, Eraso Elena, Munro Carol A, Valentín Eulogio, Mateo Estibaliz, de Groot Piet W J
Institute for Biomedicine, ETSIAMB, University of Castilla-La Mancha, 02008 Albacete, Spain.
Department of Immunology, Microbiology and Parasitology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Bilbao, Spain.
FEMS Yeast Res. 2024 Jan 9;24. doi: 10.1093/femsyr/foae039.
The drug-resistant pathogenic yeast Candidozyma auris (formerly named Candida auris) is considered a critical health problem of global importance. As the cell wall plays a crucial role in pathobiology, here we performed a detailed bioinformatic analysis of its biosynthesis in C. auris and related Candidozyma haemuli complex species using Candida albicans and Saccharomyces cerevisiae as references. Our data indicate that the cell wall architecture described for these reference yeasts is largely conserved in Candidozyma spp.; however, expansions or reductions in gene families point to subtle alterations, particularly with respect to β--1,3--glucan synthesis and remodeling, phosphomannosylation, β-mannosylation, and glycosylphosphatidylinositol (GPI) proteins. In several aspects, C. auris holds a position in between C. albicans and S. cerevisiae, consistent with being classified in a separate genus. Strikingly, among the identified putative GPI proteins in C. auris are adhesins typical for both Candida (Als and Hyr/Iff) and Saccharomyces (Flo11 and Flo5-like flocculins). Further, 26 putative C. auris GPI proteins lack homologs in Candida genus species. Phenotypic analysis of one such gene, QG37_05701, showed mild phenotypes implicating a role associated with cell wall β-1,3-glucan. Altogether, our study uncovered a wealth of information relevant for the pathogenicity of C. auris as well as targets for follow-up studies.
耐药致病酵母耳念珠菌(原名为耳道假丝酵母)被认为是一个具有全球重要性的关键健康问题。由于细胞壁在病理生物学中起着至关重要的作用,在此我们以白色念珠菌和酿酒酵母为参考,对耳念珠菌及其相关的血耳念珠菌复合种中细胞壁的生物合成进行了详细的生物信息学分析。我们的数据表明,这些参考酵母所描述的细胞壁结构在念珠菌属物种中基本保守;然而,基因家族的扩增或缩减表明存在细微变化,特别是在β-1,3-葡聚糖合成与重塑、磷酸甘露糖基化、β-甘露糖基化以及糖基磷脂酰肌醇(GPI)蛋白方面。在几个方面,耳念珠菌处于白色念珠菌和酿酒酵母之间,这与它被归类于一个单独的属相一致。引人注目的是,在耳念珠菌中鉴定出的假定GPI蛋白中,既有念珠菌典型的黏附素(Als和Hyr/Iff),也有酿酒酵母典型的黏附素(Flo11和Flo5样絮凝蛋白)。此外,26种假定的耳念珠菌GPI蛋白在念珠菌属物种中缺乏同源物。对其中一个这样的基因QG37_05701进行的表型分析显示出轻微的表型,表明其与细胞壁β-1,3-葡聚糖相关。总之,我们的研究揭示了大量与耳念珠菌致病性相关的信息以及后续研究靶点。