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是生存能力的非必需基因,但与宿主的正常相互作用所必需。

Is a Dispensable Gene for Viability but Required for Proper Interaction with the Host.

作者信息

Hernández-Chávez Marco J, Martínez-Duncker Iván, Clavijo-Giraldo Diana M, López-Ramirez Luz A, Mora-Montes Héctor M

机构信息

Departamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato, Noria Alta s/n, col. Noria Alta, C.P., Guanajuato 36050, GTO, Mexico.

Laboratorio de Glicobiología Humana y Diagnóstico Molecular, Centro de Investigación en Dinámica Celular, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, MOR, Mexico.

出版信息

J Fungi (Basel). 2024 Jul 20;10(7):502. doi: 10.3390/jof10070502.

Abstract

Candidemia is an opportunistic mycosis with high morbidity and mortality rates. Even though is the main causative agent, other species, such as , are relevant etiological agents of candidiasis and candidemia. Compared with , there is currently limited information about biological aspects, including those related to the cell wall and the interaction with the host. Currently, it is known that its cell wall contains -linked mannans, and the contribution of these structures to cell fitness has previously been addressed using cells subjected to chemical treatments or in mutants where -linked mannans and other wall components are affected. Here, we generated a ∆ null mutant, which was affected in the first step of the -linked mannosylation pathway. The null mutant was viable, contrasting with where this gene is essential. The phenotypical characterization showed that -linked mannans were required for filamentation; proper cell wall integrity and organization; biofilm formation; protein secretion; and adhesion to extracellular matrix components, in particular to fibronectin; and type I and type II collagen. When interacting with human innate immune cells, it was found that this cell wall structure is dispensable for cytokine production, but mutant cells were more phagocytosed by monocyte-derived macrophages. Furthermore, the null mutant cells showed virulence attenuation in larvae. Thus, -linked mannans are minor components of the cell wall that are involved in different aspects of ' biology.

摘要

念珠菌血症是一种发病率和死亡率都很高的机会性真菌病。尽管白色念珠菌是主要病原体,但其他念珠菌属物种,如光滑念珠菌,也是念珠菌病和念珠菌血症的相关病原体。与白色念珠菌相比,目前关于光滑念珠菌生物学特性的信息有限,包括与细胞壁以及与宿主相互作用相关的特性。目前已知其细胞壁含有O-连接甘露聚糖,此前曾通过对细胞进行化学处理或在O-连接甘露聚糖和其他细胞壁成分受影响的突变体中研究这些结构对细胞适应性的贡献。在此,我们构建了一个OCH1基因缺失突变体,该突变体在O-连接甘露糖基化途径的第一步受到影响。该基因缺失突变体是有活力的,这与白色念珠菌中该基因必不可少的情况形成对比。表型特征表明,O-连接甘露聚糖对于丝状化、适当的细胞壁完整性和组织、生物膜形成、蛋白质分泌以及对细胞外基质成分(特别是纤连蛋白)和I型及II型胶原的黏附是必需的。在与人类天然免疫细胞相互作用时,发现这种细胞壁结构对于细胞因子的产生并非必需,但突变体细胞更容易被单核细胞衍生的巨噬细胞吞噬。此外,基因缺失突变体细胞在果蝇幼虫中显示出毒力减弱。因此,O-连接甘露聚糖是细胞壁的次要成分,参与了光滑念珠菌生物学的不同方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0fc/11277967/b3809480f5ff/jof-10-00502-g001.jpg

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