Molecular Mechanisms of anti-bacterial contact-dependent growth inhibition (CDI)

接触依赖性生长抑制（CDI）抗菌的分子机制

• 批准号: 10588224
• 负责人: Christopher S. Hayes
• 金额: $ 38.93万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10588224
• 关键词: Adopted; Anti-Bacterial Agents; Attenuated; Bacteria; Binding; Biochemical; Biogenesis; Biological Assay; C-terminal; Carbohydrates; Cell Communication; Cell surface; Cells; Communication; Complex; Deposition; Development; Distributed Systems; Dyes; Ecology; Electrons; Ensure; Escherichia coli; Evolution; Family; Filament; Funding; Genetic; Gram-Negative Bacteria; Growth; Hemolysin; Immunity; Label; Length; Lipopolysaccharides; Measures; Mediating; Membrane; Membrane Proteins; Modeling; Molecular; Molecular Chaperones; Molecular Conformation; N-terminal; O Antigens; Pathway interactions; Pectobacterium; Penetration; Peptides; Play; Predisposition; Protein Secretion; Proteins; Proteus mirabilis; Pseudomonas; Research; Role; Site; Site-Directed Mutagenesis; Structure; Surface; System; Testing; Toxin; Variant; Visualization; antimicrobial; beta barrel; extracellular; functional hypothalamic amenorrhea; human pathogen; inhibitor; insight; mutation screening; nanoGold; novel; novel strategies; pathogen; pathogenic bacteria; periplasm; receptor; receptor binding; response

Bacteria have evolved complex strategies to compete and communicate with one another. One important mechanism of inter-bacterial competition is mediated by contact-dependent growth inhibition (CDI) systems. CDI systems are found in a wide variety of Gram-negative bacteria, including many important human pathogens. CDI is mediated by the CdiB-CdiA family of two-partner secretion proteins. CdiB is an Omp85 outer-membrane protein that is required for the export and assembly of CdiA effector proteins onto the cell surface. CdiA binds to receptors on susceptible bacteria and then delivers its C-terminal toxin domain (CdiA- CT) into the target cell. CDI systems also encode CdiI immunity proteins, which bind the CdiA-CT and neutralize toxin activity to protect CDI+ cells from auto-inhibition. Remarkably, CdiA-CT sequences are highly variable between bacteria, as are the corresponding CdiI immunity proteins. Current analysis indicates that CDI systems encode at least 120 distinct CDI toxin-immunity families. This application proposes a combination of genetic, biochemical and ultrastructural analyses to gain mechanistic insights into cell-cell interactions and CdiA-CT toxin delivery during CDI. This research will significantly increase our understanding of the ecology and evolution of bacterial pathogens and could inform novel approaches to antimicrobial therapy.

细菌已经进化出复杂的策略来相互竞争和交流。一个重要 细菌间竞争的机制是由接触依赖性生长抑制（CDI）系统介导的。 CDI系统存在于多种革兰氏阴性细菌中，包括许多重要的人类革兰氏阴性细菌。 病原体CDI由双伴侣分泌蛋白的CdiB-CdiA家族介导。CDIB是Omp 85 CdiA效应蛋白输出和组装到细胞上所需的外膜蛋白 面CdiA与易感细菌上的受体结合，然后递送其C-末端毒素结构域（CdiA-C）。 CT）进入靶细胞。CDI系统还编码CdiI免疫蛋白，其结合CdiA-CT， 中和毒素活性，保护CDI+细胞免受自抑制。值得注意的是，CdiA-CT序列高度 在细菌之间是可变的，相应的CdiI免疫蛋白也是如此。目前的分析表明， CDI系统编码至少120种不同的CDI毒素免疫家族。本申请提出了一种组合 遗传，生化和超微结构分析，以获得细胞间相互作用的机制见解， CDI期间的CdiA-CT毒素递送。这项研究将大大增加我们对生态学的理解 和细菌病原体的进化，并可能为抗菌治疗提供新的方法。

项目成果

Escherichia coli EC93 deploys two plasmid-encoded class I contact-dependent growth inhibition systems for antagonistic bacterial interactions.

• DOI: 10.1099/mgen.0.000534
• 发表时间: 2021-03
• 期刊: Microbial genomics
• 影响因子: 3.9
• 作者: Wäneskog M;Halvorsen T;Filek K;Xu F;Hammarlöf DL;Hayes CS;Braaten BA;Low DA;Poole SJ;Koskiniemi S
• 通讯作者: Koskiniemi S

Lipidation of Class IV CdiA Effector Proteins Promotes Target Cell Recognition during Contact-Dependent Growth Inhibition.

• DOI: 10.1128/mbio.02530-21
• 发表时间: 2021-10-26
• 期刊: mBio
• 影响因子: 6.4
• 作者: Halvorsen TM;Garza-Sánchez F;Ruhe ZC;Bartelli NL;Chan NA;Nguyen JY;Low DA;Hayes CS
• 通讯作者: Hayes CS

CdiA Effectors Use Modular Receptor-Binding Domains To Recognize Target Bacteria.

• DOI: 10.1128/mbio.00290-17
• 发表时间: 2017-03-28
• 期刊: mBio
• 影响因子: 6.4
• 作者: Ruhe ZC;Nguyen JY;Xiong J;Koskiniemi S;Beck CM;Perkins BR;Low DA;Hayes CS
• 通讯作者: Hayes CS

Non-pathogenic Escherichia coli Enhance Stx2a Production of E. coli O157:H7 Through Both bamA-Dependent and Independent Mechanisms.

• DOI: 10.3389/fmicb.2018.01325
• 发表时间: 2018
• 期刊: Frontiers in microbiology
• 影响因子: 5.2
• 作者: Xiaoli L;Figler HM;Goswami Banerjee K;Hayes CS;Dudley EG
• 通讯作者: Dudley EG

Leveraging microfluidic dielectrophoresis to distinguish compositional variations of lipopolysaccharide in E. coli.

• DOI: 10.3389/fbioe.2023.991784
• 发表时间: 2023
• 期刊: Frontiers in bioengineering and biotechnology
• 影响因子: 5.7