The UPEC pore-forming toxin α-hemolysin triggers proteolysis of host proteins to disrupt cell adhesion, inflammatory, and survival pathways.
The UPEC pore-forming toxin α-hemolysin triggers proteolysis of host proteins to disrupt cell adhesion, inflammatory, and survival pathways.
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DOI：
10.1016/j.chom.2011.12.003
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发表时间：
2012-01-19
影响因子：
30.3
通讯作者：
Mulvey MA
中科院分区：
文献类型：
--
作者：
Dhakal BK;Mulvey MA
尿路致病性大肠杆菌（UPEC）是急性和慢性尿路感染的主要原因，通常会分泌一种不稳定的成孔毒素，称为α-溶血素（HlyA）。我们发现，HlyA稳定地插入上皮细胞和巨噬细胞膜会引发细胞骨架支架蛋白paxillin和其他宿主调节蛋白的降解，以及促炎nf - κ b信号级联的成分。这些因子的蛋白水解需要宿主丝氨酸蛋白酶，而帕罗西林的降解特别涉及丝氨酸蛋白酶中-胰蛋白酶。在HlyA诱导中胰蛋白酶激活之前，中胰蛋白酶前体从细胞质沿微管和核内重新分布到灶中。HlyA中毒也刺激了半胱天冬酶的激活，其发生独立于对宿主丝氨酸蛋白酶的影响。hlya诱导的宿主蛋白水解可能使UPEC不仅可以调节上皮细胞功能，还可以使巨噬细胞失活并抑制炎症反应。
Uropathogenic Escherichia coli (UPEC), which are the leading cause of both acute and chronic urinary tract infections, often secrete a labile pore-forming toxin known as α-hemolysin (HlyA). We show that stable insertion of HlyA into epithelial cell and macrophage membranes triggers degradation of the cytoskeletal scaffolding protein paxillin and other host regulatory proteins, as well as components of the proinflammatory NFκB signaling cascade. Proteolysis of these factors requires host serine proteases, and paxillin degradation specifically involves the serine protease mesotrypsin. The induced activation of mesotrypsin by HlyA is preceded by redistribution of mesotrypsin precursors from the cytosol into foci along microtubules and within nuclei. HlyA intoxication also stimulated caspase activation, which occurred independently of effects on host serine proteases. HlyA-induced proteolysis of host proteins likely allows UPEC to not only modulate epithelial cell functions, but also disable macrophages and suppress inflammatory responses.
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影响因子：
3.1
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.0702729104
发表时间：
2007-08-14
影响因子：
11.1
作者：
Hamon, Melanie Anne;Batsche, Eric;Cossart, Pascale
通讯作者：
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