关键词: O-antigen Shigella flexneri complement polysaccharide virulence

Mesh : Animals Guinea Pigs O Antigens / genetics metabolism Serotyping Plasmids Shigella flexneri / genetics metabolism Ethanolamines

来  源:   DOI:10.1021/acsinfecdis.3c00602

Abstract:
Shigellosis poses an ongoing global public health threat. The presence and length of the O-antigen in lipopolysaccharide play critical roles in Shigella pathogenesis. The plasmid-mediated opt gene encodes a phosphoethanolamine (PEtN) transferase that catalyzes the addition of PEtN to the O-antigen of Shigella flexneri serotype X and Y strains, converting them into serotype Xv and Yv strains, respectively. Since 2002, these modified strains have become prevalent in China. Here we demonstrate that PEtN-mediated O-antigen modification in S. flexneri increase the severity of corneal infection in guinea pigs without any adaptive cost. This heightened virulence is associated with epithelial cell adhesion and invasion, as well as an enhanced inflammatory response of macrophage. Notably, PEtN addition allow S. flexneri to attenuate the binding of complement C3 and better resist phagocytosis, potentially contributing to the retention of S. flexneri in the host environment.
摘要:
志贺氏菌病构成了持续的全球公共卫生威胁。脂多糖中O-抗原的存在和长度在志贺氏菌发病机理中起关键作用。质粒介导的opt基因编码磷酸乙醇胺(PEtN)转移酶,该酶催化将PEtN添加到福氏志贺氏菌血清型X和Y菌株的O抗原中,将它们转化为血清型Xv和Yv菌株,分别。自2002年以来,这些修饰菌株已在中国流行。在这里,我们证明了PEtN介导的O抗原修饰在福氏链球菌中增加了豚鼠角膜感染的严重程度,而没有任何适应性成本。这种增加的毒力与上皮细胞粘附和侵袭有关,以及巨噬细胞的炎症反应增强。值得注意的是,PEtN的添加允许福氏链球菌减弱补体C3的结合并更好地抵抗吞噬作用,可能有助于福氏链球菌在宿主环境中的保留。
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