Pérez-García Luis A, Csonka Katalin, Flores-Carreón Arturo, Estrada-Mata Eine, Mellado-Mojica Erika, Németh Tibor, López-Ramírez Luz A, Toth Renata, López Mercedes G, Vizler Csaba, Marton Annamaria, Tóth Adél, Nosanchuk Joshua D, Gácser Attila, Mora-Montes Héctor M
Departamento de Biología, División de Ciencias Naturales y Exactas, Universidad de Guanajuato Guanajuato, Mexico.
Department of Microbiology, University of Szeged Szeged, Hungary.
Front Microbiol. 2016 Mar 8;7:306. doi: 10.3389/fmicb.2016.00306. eCollection 2016.
Candida parapsilosis is an important, emerging opportunistic fungal pathogen. Highly mannosylated fungal cell wall proteins are initial contact points with host immune systems. In Candida albicans, Och1 is a Golgi α1,6-mannosyltransferase that plays a key role in the elaboration of the N-linked mannan outer chain. Here, we disrupted C. parapsilosis OCH1 to gain insights into the contribution of N-linked mannosylation to cell fitness and to interactions with immune cells. Loss of Och1 in C. parapsilosis resulted in cellular aggregation, failure of morphogenesis, enhanced susceptibility to cell wall perturbing agents and defects in wall composition. We removed the cell wall O-linked mannans by β-elimination, and assessed the relevance of mannans during interaction with human monocytes. Results indicated that O-linked mannans are important for IL-1β stimulation in a dectin-1 and TLR4-dependent pathway; whereas both, N- and O-linked mannans are equally important ligands for TNFα and IL-6 stimulation, but neither is involved in IL-10 production. Furthermore, mice infected with C. parapsilosis och1Δ null mutant cells had significantly lower fungal burdens compared to wild-type (WT)-challenged counterparts. Therefore, our data are the first to demonstrate that C. parapsilosis N- and O-linked mannans have different roles in host interactions than those reported for C. albicans.
近平滑念珠菌是一种重要的新兴机会性真菌病原体。高度甘露糖基化的真菌细胞壁蛋白是与宿主免疫系统的初始接触点。在白色念珠菌中，Och1是一种高尔基体α1,6-甘露糖基转移酶，在N-连接甘露聚糖外链的形成中起关键作用。在这里，我们破坏了近平滑念珠菌的OCH1，以深入了解N-连接甘露糖基化对细胞适应性以及与免疫细胞相互作用的贡献。近平滑念珠菌中Och1的缺失导致细胞聚集、形态发生失败、对细胞壁干扰剂的敏感性增强以及细胞壁组成缺陷。我们通过β-消除去除了细胞壁O-连接的甘露聚糖，并评估了甘露聚糖在与人类单核细胞相互作用过程中的相关性。结果表明，O-连接的甘露聚糖在依赖于dectin-1和TLR4的途径中对IL-1β刺激很重要；而N-连接和O-连接的甘露聚糖都是TNFα和IL-6刺激的同等重要的配体，但两者都不参与IL-10的产生。此外，与野生型（WT）感染的小鼠相比，感染近平滑念珠菌och1Δ缺失突变体细胞的小鼠真菌负荷显著降低。因此，我们的数据首次证明，近平滑念珠菌N-连接和O-连接的甘露聚糖在宿主相互作用中的作用与白色念珠菌报道的不同。
