美国佛罗里达中央大学的微生物学教授Keith Ireton的科研小组发现了致死性食源性细菌一个先前未被了解的的传播机制。
李斯特氏菌(Listeria monocytogenes)是一种细菌。它会导致怀孕妇女流产,在老年人和免疫系统损伤人群中引起脑膜炎。2002年在美国多个州就爆发了利斯特氏菌病。
研究至今,科学家已经知道利斯特菌会从人类的一个细胞传递到另一个细胞,即它能够快速地感染其相邻细胞。
在这项研究中,Ireton的研究小组发现了一个之前未知的过程,该过程能够帮助细菌感染健康细胞。这项研究结果发表在本周的Nature Cell Biology上。
健康人类细胞的脂膜通常处于紧张的状态,这种状态可以阻止利斯特菌到相邻未被感染细胞的传播。然而,在实验室中,研究人员发现,利斯特菌的一种叫InIC的蛋白,似乎缓解了感染细胞脂膜的张力,使脂膜更易变形而有利于细菌的转移,随后进入相邻的健康细胞。
Ireton的实验室还发现,InIC缓解张力的方式是通过阻碍人类细胞中一种叫Tuba的蛋白的活性。Tuba正常的作用是帮助脂膜产生张力,而利斯特菌蛋白InIC阻碍了Tuba蛋白的活性,减缓了张力使细菌能够传播到附近的健康细胞。
这项关于病原菌通过控人类细胞脂膜张力进行传播的研究还没有科学文献描述,所以该发现可能有助于其他的细菌性病原菌的研究,如志贺氏菌等,同时也为未来相关疾病的治疗以及细菌性病原菌导致疾病的机制的理解开辟了道路。
研究人员指出,接下来他们还需要进行更多深入的研究。(生物谷bioon.com)
生物谷推荐原始出处:
Nature Cell Biology 20 September 2009 | doi:10.1038/ncb1964
The bacterial virulence factor InlC perturbs apical cell junctions and promotes cell-to-cell spread of Listeria
Tina Rajabian1, Balramakrishna Gavicherla2, Martin Heisig3, Stefanie Müller-Altrock4, Werner Goebel4, Scott D. Gray-Owen1 & Keith Ireton2
Several pathogenic bacteria, including Listeria monocytogenes, use an F-actin motility process to spread between mammalian cells1. Actin 'comet tails' propel Listeria through the cytoplasm, resulting in bacteria-containing membrane protrusions that are internalized by neighbouring cells. The mechanism by which Listeria overcomes cortical tension to generate protrusions is unknown. Here, we identify bacterial and host proteins that directly regulate protrusions. We show that efficient spreading between polarized epithelial cells requires the secreted Listeria virulence protein InlC (internalin C). We next identify the mammalian adaptor protein Tuba as a ligand of InlC. InlC binds to a carboxy-terminal SH3 domain in Tuba, which normally engages the human actin regulatory protein N-WASP2. InlC promotes protrusion formation by inhibiting Tuba and N-WASP activity, probably by impairing binding of N-WASP to the Tuba SH3 domain. Tuba and N-WASP are known to control the structure of apical junctions in epithelial cells3. We demonstrate that, by inhibiting Tuba and N-WASP, InlC makes taut apical junctions become slack. Experiments with myosin II inhibitors indicate that InlC-mediated perturbation of apical junctions accounts for the role of this bacterial protein in protrusion formation. Collectively, our results suggest that InlC promotes bacterial dissemination by relieving cortical tension, thereby enhancing the ability of motile bacteria to deform the plasma membrane into protrusions.
1 Department of Molecular Genetics, University of Toronto. Toronto, Ontario, M5S 1A8, Canada.
2 Department of Molecular Biology and Microbiology, College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32826-3227, USA.
3 Institute for Medical Radiation and Cell Research (MSZ), University of Würzburg, 97078, Würzburg, Germany.
4 Biocenter (Microbiology), University of Würzburg, 97074 Würzburg, Germany.