FadA from Fusobacterium nucleatum utilizes both secreted and nonsecreted forms for functional oligomerization for attachment and invasion of host cells
FadA from Fusobacterium nucleatum utilizes both secreted and nonsecreted forms for functional oligomerization for attachment and invasion of host cells
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DOI：
10.1074/jbc.m611567200
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发表时间：
2007-08-24
影响因子：
4.8
通讯作者：
Han, Yiping W.
中科院分区：
文献类型：
--
作者：
Xu, Minghua;Yamada, Mitsunori;Han, Yiping W.
具核梭杆菌是一种革兰氏阴性厌氧菌，与各种人类感染有关，包括牙周病和早产。一种新的FadA粘附素最近被确定为宿主细胞结合。它由129个氨基酸残基组成，具有18个氨基酸的信号肽。FadA在大肠杆菌中的表达增强了细菌与宿主上皮细胞和内皮细胞的结合。在E. coli和F. FadA以两种形式存在，完整的前FadA和分泌的成熟FadA（mFadA），其中前FadA锚定在细菌的内膜中，而mFadA分泌到细菌的外部。Pre-FadA和mFadA形成高M-r复合物。当将每种形式纯化成单一种类时，mFadA在中性pH下可溶，而pre-FadA不溶。当与mFadA混合或在酸性pH下时，Pre-FadA变得可溶。当将荧光标记的mFadA单独加入上皮细胞时，未检测到结合。然而，当与未标记的pre-FadA混合时，观察到mFadA结合并侵入上皮细胞。FadA是一种独特的细菌粘附素/侵袭素，因为它利用其自身的两种形式用于结构和功能目的。前FadA-mFadA复合物可能锚定在内膜中并突出穿过外膜。pre-FadA- mFadA的内化确保细菌侵入宿主细胞。
Fusobacterium nucleatum is a Gram-negative anaerobe associated with various human infections, including periodontal diseases and preterm birth. A novel FadA adhesin was recently identified for host-cell binding. It consists of 129 amino acid residues, with an 18-amino acid signal peptide. Expression of FadA in Escherichia coli enhanced bacterial binding to host epithelial and endothelial cells. In both E. coli and F. nucleatum, FadA exists in two forms, the intact pre- FadA and the secreted mature FadA ( mFadA), with pre- FadA anchored in the inner membrane and mFadA secreted outside the bacteria. Pre- FadA and mFadA formed high M-r complexes. When each form was purified to a single species, mFadA was soluble at neutral pH, whereas pre- FadA was insoluble. Pre- FadA became soluble when mixed with mFadA or under acidic pH. When fluorescence-labeled mFadA alone was added to the epithelial cells, no binding was detected. However, when mixed with nonlabeled pre- FadA, binding and invasion of mFadA into epithelial cells was observed. FadA is a unique bacterial adhesin/ invasin in that it utilizes its own two forms for both structural and functional purposes. The pre- FadA-mFadA complex is probably anchored in the inner membrane and protrudes through the outer membrane. Internalization of the pre- FadA- mFadA ensures invasion of the bacteria into the host cells.