Chen Jiexi, Goerdeler Felix, Jaroentomeechai Thapakorn, Hernandez Francisco X S, Wang Xiaozhong, Clausen Henrik, Narimatsu Yoshiki, Satchell Karla J F
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, Copenhagen, Denmark.
Sci Adv. 2025 Apr 11;11(15):eadt0063. doi: 10.1126/sciadv.adt0063. Epub 2025 Apr 9.
Multifunctional autoprocessing repeats-in-toxin (MARTX) toxins are a diverse effector delivery platform of many Gram-negative bacteria that infect mammals, insects, and aquatic animal hosts. The mechanisms by which these toxins recognize host cell surfaces have remained elusive. Here, we map a surface interaction domain of a MARTX toxin from the highly lethal foodborne pathogen . This domain corresponds to a 273-amino acid sequence with predicted symmetrical immunoglobulin-like folds. We demonstrate that this domain binds internal -acetylglucosamine on complex biantennary N-glycans with select preference for L1CAM and other N-glycoproteins with multiple N-glycans on host cell surfaces. This domain is also essential for pathogenesis during intestinal infection. The identification of a highly conserved motif universally present as part of all N-glycans correlates with the MARTX toxin having broad specificity and targeting nearly all cell types.
多功能自加工毒素重复序列（MARTX）毒素是多种革兰氏阴性细菌的一种多样的效应物递送平台，这些细菌可感染哺乳动物、昆虫和水生动物宿主。这些毒素识别宿主细胞表面的机制一直难以捉摸。在这里，我们绘制了一种来自高致死性食源性病原体的MARTX毒素的表面相互作用结构域。该结构域对应于一个273个氨基酸的序列，具有预测的对称免疫球蛋白样折叠。我们证明，该结构域与复杂双天线N-聚糖上的内部N-乙酰葡糖胺结合，对L1CAM和宿主细胞表面具有多个N-聚糖的其他N-糖蛋白有选择性偏好。该结构域对于肠道感染期间的发病机制也至关重要。作为所有N-聚糖一部分普遍存在的高度保守基序的鉴定与MARTX毒素具有广泛特异性并靶向几乎所有细胞类型相关。
