STREPTOCOCCUS PLASMIDS: MOLECULAR GENETIC ANALYSIS

链球菌质粒：分子遗传学分析

• 批准号: 3126294
• 负责人: VICKERS BURDETT
• 金额: $ 17.96万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-01-01 至 1992-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3126294
• 关键词: DNA; Streptococcus; Streptococcus infection; Streptococcus vaccine; antibacterial agents; antibiotics; bacterial genetics; bacterial proteins; communicable disease transmission; gel electrophoresis; gene expression; genetic strain; immunochemistry; laboratory rabbit; membrane proteins; mixed tissue /cell culture; mutant; nucleic acid sequence; plasmids; protein biosynthesis; ribosomes; virulence

Streptococcal diseases are among the most common bacterial infections in man. One approach to the control of infectious diseases is the use of antibacterial drugs. Our studies have previously identified three tetracycline resistance determinants and have shown that two of these determinants (tetM and tetN) mediate resistance by a novel mechanism involving a cytoplasmic factor which associates with ribosomes and renders protein synthesis resistant to the drug. The tetM determinant may be particularly significant in chemical terms since it has been identified in a number of other bacterial pathogens. Elucidation of the basis of tetM mediated resistance will provide information not only about this resistance mechanism but also about ribosome function and response to antibiotics during protein synthesis. We will purify the resistance factor and characterize its interaction with ribosomes and investigate the biochemical basis of tetM action. The tetN determinant will be cloned and the resistance region defined using deletion analysis and insertion mutagenesis. The tetN gene products will be analyzed in minicells and by in vitro translation. Vaccines are also useful in control of infectious diseases. M- protein is a surface protein associated with virulence of group A streptococcus and antibodies directed against this protein protect the host against subsequent infection by the same group A streptococcal serotype. To begin molecular characterization of this protein, we have cloned and sequenced the serotype 24 M- protein gene of group A streptococcus. The mature M-protein is novel in that it contains several highly conserved repeated sequences; the carboxyl terminal portion of the protein is also conserved among different serotypes. These latter regions of the M-24 protein can be specifically overproduced and tested for their ability to elicit protective antibodies against a variety of M- protein serotypes.

链球菌疾病是最常见的细菌之一 人类感染。 一种控制传染性的方法 疾病是使用抗菌药物。 我们的研究有 先前确定的三个四环素抗性决定因素 并显示了这些决定因素中的两个（TETM和TETN） 通过涉及细胞质的新机制介导抗性 与核糖体和渲染蛋白相关的因素 对药物的抗合成性。 TETM决定因素可能是 在化学方面特别重要，因为它已经 在许多其他细菌病原体中鉴定出来。 阐明 TETM介导的电阻的基础将提供信息 不仅与这种抗性机制有关，还与核糖体有关 蛋白质合成过程中对抗生素的功能和反应。 我们 将净化电阻因子并表征其相互作用 与核糖体一起研究TETM的生化基础 行动。 TETN的决定因素将被克隆并电阻 使用缺失分析和插入诱变定义的区域。 TETN基因产物将在微型币和IN中进行分析 体外翻译。 疫苗也可用于控制传染病。 m- 蛋白质是与A组毒力相关的表面蛋白 针对该蛋白保护的链球菌和抗体 同一组A反对随后感染的宿主 链球菌血清型。 开始分子表征 我们已经克隆并测序了24 m-的血清型 A组链球菌的蛋白质基因。 成熟的M蛋白是 小说中，它包含几个高度保守的重复 序列；蛋白质的羧基末端部分也是 在不同的血清型中保守。 这些后一个地区 M-24蛋白可以专门生产并测试其 能够引起针对各种M-的保护性抗体 蛋白质血清型。