CONJUGAL TRANSFER OF BACTERIODES ANTIBIOTIC RESISTANCES

许多人结肠类杆菌携带结合四环素 电阻(TCR)元件。一些只转移TCR，而另一些则联合- 转移TCR和编码红霉素抗性(EMR)的基因 编码EMR的同一基因也编码抗药性 克林霉素，为数不多的有效治疗的抗生素之一 类杆菌感染。类杆菌Tcr和TcrEmr元素是 被认为位于染色体中，而不是携带在质粒上。 这些元素中的大多数有一个不同寻常的特征，即频率 四环素对细菌的转移率和耐药性水平有调节作用。 最近，我们还展示了一些元素调节 四环素依赖的质粒样形式的出现，一种活性 可能与切除和转移元素本身有关。 使用我们构建的大肠杆菌-类杆菌穿梭宇宙粒，我们有 克隆了类杆菌TcrEmr元件的部分基因。我们的克隆体含有基因 元素的所有已知活动。这些克隆使之成为可能 首次研究类杆菌结合蛋白TCR元件 在分子水平上。这个项目的长期目标是 确定元件的基因组织、TCR、转移和 Exisase基因是受调控的，哪些步骤涉及切除和 染色体中元件的重新整合，以及TCR是否 不同类杆菌临床分离株中发现的成分密切相关 相关的。我们还将继续调查一种不寻常的四环素 耐药性(在类杆菌中发现，但只在 需氧培养的大肠杆菌。最近我们已经证明了这个基因编码 一种能使四环素失活的蛋白质。我们将尝试确定 灭活的四环素。我们还将对该基因及其 上游地区。尽管该基因的表达不受 四环素，上游区域的缺失影响水平 抵抗。来自序列的信息可能有助于解决该序列的作用 这个地区。

Many strains of human colonic Bacteroides carry conjugal tetracycline resistance (Tcr) elements. Some transfer Tcr only, whereas others co- transfer Tcr and a gene that codes for resistance to erythromycin (Emr) The same gene that codes for Emr also codes for resistance to clindamycin, one of the few antibiotics that is effective for treating Bacteroides infections. The Bacteroides Tcr and TcrEmr elements are thought to be located in the chromosome rather than carried on plasmids. An unusual feature of most of these elements is that both the frequency of transfer and the level of resistance are regulated by tetracycline. Recently, we have also shown that some of the elements mediate the tetracycline-dependent appearance of plasmid-like forms, an activity that could be associated with excision and transfer of the element itself. Using a n E. coli-Bacteroides shuttle cosmid we constructed, we have cloned portions of a Bacteroides TcrEmr element. Our clones contain genes for all known activities of the element. These clones make it possible for the first time to investigate the conjugal Bacteroides Tcr elements at the molecular level. The long term goal of this project is to determine the gene organization of the element, how the Tcr, transfer and excisase genes are regulated, what steps are involved in excision and reintegration of the element in the chromosome, and whether the Tcr elements found in different Bacteroides clinical isolates are closely related. We will also continue to investigate an unusual tetracycline resistance ( which was found in Bacteroides but which works only in aerobically grown E. coli. Recently we have shown that this gene codes for a protein that inactivates tetracycline. We will try to identify the inactivated form of tetracycline. We will also sequence the gene and its upstream region. Although expression of the gene is not regulated by tetracycline, deletions in the upstream region affect the level of resistance. Information from the sequence may help to resolve the role of this region.