Conjugal Transfer of Bacteroides Antibiotic Resistances

拟杆菌抗生素耐药性的夫妻转移

• 批准号: 6736865
• 负责人: Abigail A Salyers
• 金额: $ 26.78万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6736865
• 关键词: Bacteroides; bacterial genetics; drug resistance; gene expression; gene interaction; genetic regulation; genetic regulatory element; microorganism conjugation; transfection; transposon /insertion element

DESCRIPTION (provided by applicant): The incidence of antibiotic resistance is increasing in many groups of disease-causing bacteria. Although some bacteria become resistant to antibiotics through mutation, acquisition of antibiotic resistance genes from other bacteria is probably more common. This proposal focuses on the genus Bacteroides. Bacteroides species are among the numerically predominant species of bacteria in the human colon. Bacteroides species are also opportunistic pathogens that can cause life-threatening infections. Many Bacteroides strains have become resistant to multiple antibiotics. Transfer of resistance genes among these strains appears to have occurred mainly through the actions of a group of conjugative transposons (CTns), represented by CTnDOT. CTnDOT excises from the chromosome to form a circular intermediate, which transfers by conjugation to a recipient and integrates into the recipient's chromosome. During the previous funding period, genes responsible for excision and transfer were identified and shown to be controlled by a complex set of regulatory genes. These genes may allow the CTn to coordinate excision and transfer so that nicking to initiate transfer of the circular form does not occur until excision is complete. Both excision and transfer are stimulated over 1,000-fold by the antibiotic tetracycline. Previously, we found that three genes, rteA, rteB and rteC function as central regulatory genes. We propose that RteC triggers expression of two excision genes, excA and excB. The first specific aim of the proposal is to test this hypothesis. The second aim is to determine how ExcA and ExcB, presumably in concert with the CTn integrase (Int), catalyze excision and circularization of the CTn. The third specific aim is to determine whether RteC also controls expression of a gene currently designated as orf5 and to test the hypothesis that Orf5 in turn controls the expression of transfer (tra) genes. The fourth specific aim is to answer the question of how effective coordination of excision and transfer actually is. The last aim is to define the characteristics and functions of RteA and RteB, which control expression of rteC.

描述（由申请人提供）： 抗生素耐药性的发生率是 许多致病细菌群不断增加。虽然有些细菌 通过突变、获得抗生素而对抗生素产生耐药性 来自其他细菌的耐药基因可能更常见。这个提议 重点关注拟杆菌属。拟杆菌属数量众多 人类结肠中的主要细菌种类。拟杆菌属物种有 也可能导致危及生命的感染的机会病原体。许多 拟杆菌菌株已对多种抗生素产生耐药性。转让 这些菌株中的抗性基因似乎主要是通过 一组接合转座子 (CTns) 的作用，表示为 CTnDOT。 CTnDOT从染色体上切除形成环状中间体， 它通过缀合转移到受体并整合到 受体的染色体。在上一个资助期间，基因负责 切除和转移的过程已被识别并显示由 一组复杂的调控基因。这些基因可能允许 CTn 协调 切除和转移，以便切口以启动圆形形式的转移 直到切除完成后才会发生。切除和转移都是 抗生素四环素的刺激超过 1,000 倍。此前，我们发现 rteA、rteB 和 rteC 三个基因作为中央调控基因。我们 提出 RteC 触发两个切除基因 excA 和 excB 的表达。这 该提案的第一个具体目标是检验这一假设。第二个目标 是确定 ExcA 和 ExcB 如何与 CTn 整合酶协同作用 (Int)，催化 CTn 的切除和环化。第三个具体目标 确定RteC当前是否也控制基因的表达 指定为 orf5 并检验 Orf5 依次控制的假设 转移（tra）基因的表达。第四个具体目标是回答 切除和转移的协调实际上如何有效的问题。 最后的目的是定义RteA和RteB的特性和功能， 其控制 rteC 的表达。