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: 10360608
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10360608
• 关键词: Adopted; Anti-Bacterial Agents; Attenuated; Bacteria; Bacterial Toxins; Binding; Biochemical; Biogenesis; Biological Assay; C-terminal; Carbohydrates; Cell Communication; Cell surface; Cells; 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; Peptides; Play; Protein Secretion; Proteins; Proteus mirabilis; Pseudomonas; Research; Role; Site; Site-Directed Mutagenesis; Structure; Surface; System; Testing; Toxin; Variant; antimicrobial; extracellular; functional hypothalamic amenorrhea; human pathogen; inhibitor; insight; mutation screening; nanoGold; novel; novel strategies; pathogen; pathogenic bacteria; periplasm; receptor; receptor binding; response; tyrosyl-proline

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.

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