Mechanical stress compromises multicomponent efflux complexes in bacteria
Mechanical stress compromises multicomponent efflux complexes in bacteria
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DOI：
10.1073/pnas.1909562116
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发表时间：
2019-12-17
影响因子：
11.1
通讯作者：
Hernandez, Christopher J.
中科院分区：
文献类型：
--
作者：
Genova, Lauren A.;Roberts, Melanie F.;Hernandez, Christopher J.
物理力对生物体的生长、形态、运动和生存有着深远的影响。在单个细胞的水平上，机械力的作用在真核生物生理学中得到了很好的认识，但对原核生物的了解要少得多。最近的研究结果表明物理力对细菌形状，细胞分裂，运动性，毒力和生物膜起始的影响，但仍不清楚施加于细菌的机械力如何在分子水平上翻译。在革兰氏阴性细菌中，多组分蛋白质复合物可以在细胞包膜上形成刚性连接，因此受到细胞所经历的物理力的影响。在这里，我们操纵拉伸和剪切机械应力在细菌细胞的信封，并使用单分子跟踪表明，八面体剪切（但不是流体静力学）应力内的细胞信封促进拆卸的三方外排复合体CusCBA，大肠杆菌用于抵抗铜和银毒性的系统。通过促进这种蛋白质复合物的分解，细胞包膜内的机械力使细菌更容易受到金属毒性的影响。这些研究结果表明，机械力可以抑制细菌中细胞包膜蛋白组装体的功能，并表明其他多组分，transenvelope外排复合物可能对机械力敏感，包括涉及抗生素耐药性，细胞分裂和外膜成分易位的复合物。通过调节细胞包膜内蛋白质的功能，机械应力具有调节细菌存活和生长所需的多个过程的潜力。
Physical forces have a profound effect on growth, morphology, locomotion, and survival of organisms. At the level of individual cells, the role of mechanical forces is well recognized in eukaryotic physiology, but much less is known about prokaryotic organisms. Recent findings suggest an effect of physical forces on bacterial shape, cell division, motility, virulence, and biofilm initiation, but it remains unclear how mechanical forces applied to a bacterium are translated at the molecular level. In Gram-negative bacteria, multicomponent protein complexes can form rigid links across the cell envelope and are therefore subject to physical forces experienced by the cell. Here we manipulate tensile and shear mechanical stress in the bacterial cell envelope and use single-molecule tracking to show that octahedral shear (but not hydrostatic) stress within the cell envelope promotes disassembly of the tripartite efflux complex CusCBA, a system used by Escherichia coli to resist copper and silver toxicity. By promoting disassembly of this protein complex, mechanical forces within the cell envelope make the bacteria more susceptible to metal toxicity. These findings demonstrate that mechanical forces can inhibit the function of cell envelope protein assemblies in bacteria and suggest the possibility that other multicomponent, transenvelope efflux complexes may be sensitive to mechanical forces including complexes involved in antibiotic resistance, cell division, and translocation of outer membrane components. By modulating the function of proteins within the cell envelope, mechanical stress has the potential to regulate multiple processes required for bacterial survival and growth.