N-acetyllactosamine-induced retraction of bundle-forming pili regulates virulence-associated gene expression in enteropathogenic Escherichia coli.

N-acetyllactosamine-induced retraction of bundle-forming pili regulates virulence-associated gene expression in enteropathogenic Escherichia coli.
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DOI:
10.1111/j.1365-2958.2010.07192.x
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发表时间:
2010-06-01
影响因子:
3.6
通讯作者:
Armstrong GD
Armstrong GD
中科院分区:
生物学2区
文献类型:
--
作者:
Humphries RM;Griener TP;Vogt SL;Mulvey GL;Raivio T;Donnenberg MS;Kitov PI;Surette M;Armstrong GD

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肠致病性大肠杆菌是发展中国家婴儿腹泻发病和死亡的主要原因。EPEC的发病机制依赖于一个协调的多步骤过程,最终导致生物体与宿主肠粘膜的紧密粘附。在EPEC定殖过程的初始阶段,菌毛粘附素,即形成菌毛的皮利(BFP),起着不可或缺的作用。我们以前报道过,BFP的主要结构亚基,BFP蛋白,显示凝集素样的性质,使BFP最初系EPEC的N-乙酰乳糖胺(LacNAc)聚糖受体在宿主细胞表面。我们还报道,孵育EPEC与合成的LacNAc轴承neoglycoconjugates不仅抑制其粘附到宿主细胞,但也诱导BFP收缩和随后的降解的EPEC蛋白亚基。在此,我们证明,周质丝氨酸蛋白酶,DegP,是需要在这个过程中降解的refleclin。我们还表明,DegP似乎在BFP组装过程中作为一种蛋白伴侣,LacNAc-BSA诱导的BFP回缩之后是BFP操纵子的转录上调和EPEC中肠上皮细胞擦除操纵子的基因座的下调。
Enteropathogenic Escherichia coli (EPEC) are a major cause of infant morbidity and mortality due to diarrhoea in developing countries. The pathogenesis of EPEC is dependent on a coordinated multi-step process culminating in the intimate adherence of the organisms to the host's intestinal mucosa. During the initial stages of the EPEC colonization process, the fimbrial adhesin, bundle-forming pili (BFP), plays an integral role. We previously reported that the major BFP structural subunit, bundlin, displays lectin-like properties which enables BFP to initially tether EPEC to N-acetyllactosamine (LacNAc) glycan receptors on host cell surfaces. We also reported that incubating EPEC with synthetic LacNAc-bearing neoglycoconjugates not only inhibits their adherence to host cells, but also induces BFP retraction and subsequent degradation of the bundlin subunits. Herein, we demonstrate that the periplasmic serine protease, DegP, is required for degrading bundlin during this process. We also show that DegP appears to act as a bundlin chaperone during BFP assembly and that LacNAc-BSA-induced BFP retraction is followed by transcriptional up-regulation of the BFP operon and down-regulation of the locus of enterocyte effacement operons in EPEC.
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