Deficiency of GPI Glycan Modification by Ethanolamine Phosphate Results in Increased Adhesion and Immune Resistance of Aspergillus fumigatus

Frontiers in Cellular and Infection Microbiology

Xiaowen Wang¹  Ruoyu Li¹  Yi Zhang¹  Yubo Ma¹  Cheng Jin²  Hui Zhou²  Jinghua Yang²  Haomiao Ouyang² 

[1] Department of Dermatology and Venerology, Peking University First Hospital, Beijing, China;Research Center for Medical Mycology, Peking University, Beijing, China;Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Peking University First Hospital, Beijing, China;National Clinical Research Center for Skin and Immune Diseases, Peking University First Hospital, Beijing, China;State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China;

关键词: Aspergillus fumigatus;    GPI anchoring;    adhesion;    virulence;    immune response;    phosphoethanolamine;    inflammation;    macrophage killing;   

DOI  :  10.3389/fcimb.2021.780959

来源: Frontiers

【 摘 要 】

Glycosylphosphatidylinositol (GPI)-anchored proteins play important roles in maintaining the function of the cell wall and participating in pathogenic processes. The addition and removal of phosphoethanolamine (EtN-P) on the second mannose residue in the GPI anchor are vital for maturation and sorting of GPI-anchored proteins. Previously, we have shown that deletion of the gpi7, the gene that encodes an EtN-P transferase responsible for the addition of EtN-P to the second mannose residue of the GPI anchor, leads to the mislocalization of GPI-anchored proteins, abnormal polarity, reduced conidiation, and fast germination in Aspergillus fumigatus. In this report, the adherence and virulence of the A. fumigatus gpi7 deletion mutant were further investigated. The germinating conidia of the mutant exhibited an increased adhesion and a higher exposure of cell wall polysaccharides. Although the virulence was not affected, an increased adherence and a stronger inflammation response of the mutant were documented in an immunocompromised mouse model. An in vitro assay confirmed that the Δgpi7 mutant induced a stronger immune response and was more resistant to killing. Our findings, for the first time, demonstrate that in A. fumigatus, GPI anchoring is required for proper organization of the conidial cell wall. The lack of Gpi7 leads to fast germination, stronger immune response, and resistance to macrophage killing.

【 授权许可】

CC BY