Reducing Virulence Through the Suppression of Retractile Pili

通过抑制回缩菌毛降低毒力

• 批准号: 10312144
• 负责人: Lanying Zeng
• 金额: $ 17.84万
• 依托单位: TEXAS A&M AGRILIFE RESEARCH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-04 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10312144
• 关键词: Acinetobacter; Anti-Bacterial Agents; Antibiotic Resistance; Bacterial Infections; Bacterial Pili; Bacteriophages; Binding; Cell Adhesion; Cells; Cryoelectron Microscopy; DNA; Data; Drug resistance; Engineering; Enterobacteria phage MS2; Escherichia coli; Fluorescence; Fluorescence Microscopy; Gene Proteins; Goals; Growth; Health; Infection; Mediating; Methods; Microbial Biofilms; Microfluidic Microchips; Molecular; Multi-Drug Resistance; Pilum; Proteins; Pseudomonas; Pseudomonas aeruginosa; Public Health; RNA; RNA Phages; Resistance development; Structural Models; System; Type IV Secretion System Pathway; Virulence; Virulence Factors; Virus-like particle; base; cell motility; density; design; genomic RNA; innovation; kinetosome; mutant; novel; novel strategies; particle; pathogen; pathogenic bacteria; pressure; receptor; resistance gene

PROJECT SUMMARY Multidrug-resistant bacterial infection is becoming a health crisis worldwide. Treatments for previously “untreatable” bacterial infection have been the spotlights of antibacterial studies, including minimizing the emergence, spread and persistence of drug-resistance genes, as well as directly neutralizing virulence factors. Many of these bacterial pathogens possess retractile pili, which are either part of secretion systems required for gene/protein transfer, or responsible for virulence. In this project, it is proposed to manipulate pili through ssRNA phages as an anti-virulence strategy against pathogenic bacteria and/or dissemination of antibiotic resistance genes. From the preliminary data, the infection of ssRNA phage MS2 or Qβ was found to cause the detachment of E. coli conjugative F-pilus through single-cell studies using fluorescence microscopy. Aim 1 is to examine the F-pili detachment efficiency by varying different mutants of Type IV section systems and growth conditions, and investigate how to reach 100% detachment efficiency. In addition, the study will be expanded to other types of retractile pili and their ssRNA phage systems for pili detachment. Aim 2 is to identify the essential components of ssRNA phages for F-pilus detachment and design novel minimal systems or virus-like particles to efficiently detach the F-pilus.

项目摘要 多重耐药细菌感染正在成为世界范围内的健康危机。以前的治疗 “无法治愈的”细菌感染一直是抗菌研究的焦点，包括最大限度地减少 耐药基因的出现、传播和持续，以及直接中和毒力因子。 这些细菌病原体中的许多具有可伸缩的皮利，这是所需的分泌系统的一部分 基因/蛋白质转移，或负责毒力。在本项目中，建议通过以下方式操纵皮利： ssRNA介导作为针对病原菌和/或抗生素传播的抗毒力策略 抗性基因根据初步数据，发现ssRNA噬菌体MS 2或Qβ的感染引起了 分离E.大肠杆菌接合F菌毛通过单细胞研究，使用荧光显微镜。目标1是 通过改变IV型切片系统和生长的不同突变体来检查F-菌毛分离效率 条件，并研究如何达到100%的分离效率。此外，该研究还将扩大 其他类型的可伸缩皮利及其用于皮利分离的ssRNA噬菌体系统。目标2是确定 ssRNA的基本成分，用于F-菌毛分离和设计新的最小系统或病毒样 颗粒以有效地分离F菌毛。

项目成果

Recent Advances in Structural Studies of Single-Stranded RNA Bacteriophages.

• DOI: 10.3390/v15101985
• 发表时间: 2023-09-23
• 期刊: Viruses
• 作者: Thongchol J;Lill Z;Hoover Z;Zhang J
• 通讯作者: Zhang J