Interaction of ipa proteins of Shigella flexneri with alpha(5)beta(1) integrin promotes entry of the bacteria into mammalian cells

被引:172
作者
Watarai, M
Funato, S
Sasakawa, C
机构
[1] UNIV TOKYO, INST MED SCI, DEPT BACTERIOL, MINATO KU, TOKYO 108, JAPAN
[2] NIPPON BIORAD LABS, MICROSCI DIV, ANAKAWA KU, TOKYO 116, JAPAN
关键词
D O I
10.1084/jem.183.3.991
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Shigella is a genus of highly adapted bacterial pathogens that cause bacillary dysentery in humans. Bacteria reaching the colon invade intestinal epithelial cells by a process of bacterial-directed endocytosis mediated by the Ipa proteins: IpaB, IpaC, and IpaD of Shigella. The invasion of epithelial cells is thought to be a receptor-mediated phenomenon, although the cellular components of the host that interact with the Ipa proteins have not yet been identified. We report here that in a Shigella flexneri invasive system and Chinese hamster ovary (CHO) cell monolayers, the Ipa proteins were capable of interacting directly with alpha(5) beta(1) integrin. The invasive capacity of S. flexneri for CHO cells increased as levels of alpha(5) beta(1) integrin were elevated. When CHO cells were infected with S. flexneri, the tyrosine phosphorylation both of pp 125(FAK), an integrin-regulated 125 K focal adhesion kinase, and of paxillin was stimulated. In contrast, an isogenic strain of S. flexneri that was defective in invasion owing to a mutation in its spa32 gene failed to induce such phosphorylation. Under in vitro and in vivo conditions, the released IpaB, IpaC, and IpaD proteins bound to alpha(5) beta(1) integrin in a manner different from that of soluble fibronectin but similar to that of the tissue form of fibronectin. At the site of attachment of S. flexneri to CHO cells, alpha(5) beta(1) integrin converged with polymerization of actin. These data thus suggest that the capacity of Ipa proteins to interact with alpha(5) beta(1) integrin may be an important Shigella factor in triggering the reorganization of actin cytoskeletons.
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页码:991 / 999
页数:9
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