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Nature新发现解答生物学谜题

摘要 : 革兰氏阴性菌可以生活在非常广泛的环境中,举例来说,大肠杆菌E.coli既可以生活在河水里也能生活在人类和动物体内。那么这些细菌是如何快速适应生长环境的改变呢?牛津大学和约克大学的研究团队在六月十日的Nature杂志上解答了这个问题。

 革兰氏阴性菌是造成感染性疾病的主要致病菌,它们的外膜可以抵御免疫系统和特定抗生素。这类细菌可以生活在非常广泛的环境中,举例来说,大肠杆菌E.coli既可以生活在河水里也能生活在人类和动物体内。

这些细菌是如何快速适应生长环境的改变呢?牛津大学和约克大学的研究团队在六月十日的Nature杂志上解答了这个问题。

为了确保自己的外膜蛋白(OMP)能够正确适应当前的生活环境,细菌采用了复杂的调控机制。不过在此之前,人们并不清楚OMP更新换代的具体机制。

Colin Kleanthous教授和Dr Christoph Baumann领导研究人员,将发荧光的大肠杆菌素(某些E.coli生产的毒素)当作OMP探针,通过单分子荧光显微镜观察OMP在外膜上的独特行为。

研究显示,数百个OMP在外膜上聚集起来,形成“OMP岛”。研究人员随后用纯化蛋白和人工膜系统模拟这一过程,发现OMP本身就有自我关联的倾向。

这项研究还在OMP岛鉴定到了重要的分子机器,负责将新OMP插入细胞膜。“找到这样的分子机器很正常,但我们完全没想到这个机器在外膜成熟后就关闭了,”Dr Baumann解释道。虽然还不清楚原因,不过这一机制是很重要的,让新OMP和老OMP不混杂在一起。

研究人员还发现,OMP生成是有梯度的,在细胞中部水平最高,在细胞两端几乎没有。随着细胞的生长,新OMP插入细胞中部,老OMP被推向两端。在两次细胞分裂之后,新生细胞上就没有任何老OMP了。换句话说,E. coli这样的细菌可以在两代之内改变外膜蛋白。

研究指出,在革兰氏阴性菌E. coli中,OMP的生成和更替是两个密不可分的过程。在OMP快速更替的同时,老OMP依然存在于细胞群体中,成为过去的“记忆”。

这些发现将产生重要的影响,有助于人们重新认识细胞外膜。研究人员指出,这项研究打开了一些新的研究方向,也为人们提供了抗生素研发的新靶标,比如说可以想办法破坏OMP岛

原文标题:Supramolecular assemblies underpin turnover of outer membrane proteins in bacteria

原文摘要:Gram-negative bacteria inhabit a broad range of ecological niches. For Escherichia coli, this includes river water as well as humans and animals, wher it can be both a commensal and a pathogen1, 2, 3. Intricate regulatory mechanisms ensure that bacteria have the right complement of β-barrel outer membrane proteins (OMPs) to enable adaptation to a particular habitat4, 5. Yet no mechanism is known for replacing OMPs in the outer membrane, an issue that is further confounded by the lack of an energy source and the high stability6 and abundance of OMPs5. Here we uncover the process underpinning OMP turnover in E. coli and show it to be passive and binary in nature, in which old OMPs are displaced to the poles of growing cells as new OMPs take their place. Using fluorescent colicins as OMP-specific probes, in combination with ensemble and single-molecule fluorescence microscopy in vivo and in vitro, as well as molecular dynamics simulations, we established the mechanism for binary OMP partitioning. OMPs clustered to form ~0.5-μm diameter islands, wher their diffusion is restricted by promiscuous interactions with other OMPs. OMP islands were distributed throughout the cell and contained the Bam complex, which catalyses the insertion of OMPs in the outer membrane7, 8. However, OMP biogenesis occurred as a gradient that was highest at mid-cell but largely absent at cell poles. The cumulative effect is to push old OMP islands towards the poles of growing cells, leading to a binary distribution when cells divide. Hence, the outer membrane of a Gram-negative bacterium is a spatially and temporally organized structure, and this organization lies at the heart of how OMPs are turned over in the membrane.

来源: Nature 浏览次数:0

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