Formation and function of cell curvature in Vibrio cholerae

霍乱弧菌细胞曲率的形成和功能

基本信息

  • 批准号:
    10443303
  • 负责人:
  • 金额:
    $ 32.46万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-07-07 至 2026-04-30
  • 项目状态:
    未结题

项目摘要

Curved bacteria represent one of the most common of bacterial shapes yet the mechanisms by which bacteria become curved and the functions of curvature are largely unknown. In addition, large-scale polymers assemble in both the cytoplasm and periplasm yet only the cytoplasmic polymers have been well characterized to date. This is an important distinction, as periplasmic proteins must contend with different molecular environments like oxidizing conditions and a lack of ATP/GTP energy sources. My lab recently demonstrated that two proteins, CrvA and CrvB, assemble into periplasmic structures that are essential for establishing cell curvature in the pathogen, Vibrio cholerae. Here we propose to leverage this system to address the field’s gaps in understanding both curved shapes and periplasmic polymer formation. In previous work, we identified and characterized the first curvature determinant in V. cholerae, CrvA. CrvA forms polymers in the periplasm that pattern the insertion of new cell wall to cause these bacteria to curve. More recently we discovered a second curvature determinant, CrvB. CrvA and CrvB colocalize in the V. cholerae periplasm, and CrvA and CrvB co-expression are sufficient to induce curvature in straight Vibrio species, E. coli, P. aeruginosa, and even distantly-related C. crescentus and A. tumefaciens. Here we seek to better understand bacterial curvature determination and function by answering three outstanding questions in three aims. 1) How do CrvA/B assemble in the periplasm, whose oxidizing conditions and lack of ATP/GTP make it a very different environment from the cytoplasm where well-characterized cytoskeletons assemble? Aim 1 will answer this question by combining electron and fluorescence microscopy to determine the structure and dynamics of CrvA/CrvB assembly. 2) How do CrvAB actually generate cell curvature? CrvAB are distinct from previously-characterized shape determinants in both being periplasmic and functioning autonomously of other shape-patterning elements like MreB. Aim 2 will thus address how CrvA and CrvB induce curvature by identifying and characterizing their interactions with the cell wall and other partners. 3) How does curvature affect bacterial behaviors? Aim 3 will harness our ability to synthetically curve bacteria and use single-cell imaging to determine how curvature affects motility in gels, biofilms, and on surfaces. These experiments will dissect the biophysical basis of important behaviors that result from cell curvature. Together these studies will establish V. cholerae CrvAB as a powerful model system for studying cell shape across multiple scales, answering fundamental questions to advance several fields. First, at the molecular scale, we will learn how polymers form in the periplasm. Second, at the cellular scale, we will learn how two proteins can curve an immense range of bacteria. And third, at the behavioral/evolutionary scale, we will learn the benefits conferred by one of the most common of bacterial shapes.
弯曲的细菌代表了最常见的细菌形状之一,但其机制

项目成果

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Zemer Gitai其他文献

Zemer Gitai的其他文献

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{{ truncateString('Zemer Gitai', 18)}}的其他基金

Formation and function of cell curvature in Vibrio cholerae
霍乱弧菌细胞曲率的形成和功能
  • 批准号:
    10661553
  • 财政年份:
    2022
  • 资助金额:
    $ 32.46万
  • 项目类别:
Mechano-microbiology: how physical forces control bacterial-host interactions
机械微生物学:物理力如何控制细菌与宿主的相互作用
  • 批准号:
    9140003
  • 财政年份:
    2015
  • 资助金额:
    $ 32.46万
  • 项目类别:
Caulobacter cell shape and cytoskeletal regulation
柄杆菌细胞形状和细胞骨架调节
  • 批准号:
    8560432
  • 财政年份:
    2013
  • 资助金额:
    $ 32.46万
  • 项目类别:
Caulobacter cell shape and cytoskeletal regulation
柄杆菌细胞形状和细胞骨架调节
  • 批准号:
    8860201
  • 财政年份:
    2013
  • 资助金额:
    $ 32.46万
  • 项目类别:
Caulobacter cell shape and cytoskeletal regulation
柄杆菌细胞形状和细胞骨架调节
  • 批准号:
    8723866
  • 财政年份:
    2013
  • 资助金额:
    $ 32.46万
  • 项目类别:
Predoctoral Training in Genetics and Molecular Biology
遗传学和分子生物学博士前培训
  • 批准号:
    8691828
  • 财政年份:
    1977
  • 资助金额:
    $ 32.46万
  • 项目类别:
Predoctoral Training in Genetics and Molecular Biology
遗传学和分子生物学博士前培训
  • 批准号:
    9306146
  • 财政年份:
    1977
  • 资助金额:
    $ 32.46万
  • 项目类别:

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