Toxoplasma chitinase- like protein orchestrates cyst wall glycosylation to facilitate effector export and cyst turnover

• 成果类型: Article
• 署名作者: Fu, Yong; Tomita, Tadakimi; Weiss, Louis M.; West, Christopher M.; Sibley, L. David
• 署名单位: Washington University (WUSTL); Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; University System of Georgia; University of Georgia
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13386
• DOI: 10.1073/pnas.241687012
• 发表日期: 2025-02-04
• 关键词: host-cells; gondii; gamma; rupture; EXIT

摘要

Toxoplasma bradyzoites reside in tissue cysts that undergo cycles of expansion, rupture, and release to foster chronic infection. The glycosylated cyst wall acts as a protective barrier, although the processes responsible for formation, remodeling, and turnover are not understood. Herein, we identify a noncanonical chitinase- like enzyme TgCLP1 that localizes to micronemes and is targeted to the cyst wall after secretion. Genetic deletion of TgCLP1 resulted in a thickened cyst wall that decreased cyst turnover, blocked the export of virulence effectors into host cells, and resulted in failure to persist during chronic infection. Genetic complementation with a series of mutants revealed that the GH19 glycosidase domain was crucial for regulating glycosylation of several glycoproteins in the cyst wall. Overall, our findings reveal that TgCLP1 is a multifunctional survival factor that modifies glyco-proteins within the cyst wall to modulate export of virulence effectors and regulate turnover of tissue cysts.