CONJUGAL TRANSFER OF BACTERIODES ANTIBIOTIC RESISTANCES

许多人结肠类杆菌携带四环素结合蛋白 电阻（Tcr）元件。有些人只转移Tcr，而另一些人则共同转移Tcr。 转移Tcr和编码红霉素抗性（Emr）的基因 编码Emr的同一基因也编码对 克林霉素是少数几种有效治疗癌症的抗生素之一， 类杆菌感染。拟杆菌Tcr和TcrEmr元件是 被认为位于染色体中而不是由质粒携带。 大多数这些元素的一个不寻常的特征是， 四环素对转移和耐药水平有调节作用。 最近，我们还表明，一些元素介导的 四环素依赖性质粒样形式的出现， 可能与元素本身的切除和转移有关。 使用一个N E。我们构建的coli-Bacteroides穿梭粘粒， 拟杆菌TcrEmr元件的克隆部分。我们的克隆体含有 元素的所有已知活动。这些克隆人使我们有可能 首次对拟杆菌Tcr结合元件进行了研究 在分子水平上。该项目的长期目标是 确定元件的基因组织，Tcr如何转移和 切除酶基因的调控，切除涉及哪些步骤， 染色体中的元件的重新整合，以及Tcr是否 在不同的拟杆菌临床分离株中发现的元素是密切相关的， 相关.我们还将继续调查一种不寻常的四环素 耐药性（在拟杆菌中发现，但仅在 有氧生长的E.杆菌最近，我们已经证明，这种基因编码 一种能使四环素失活的蛋白质我们将尝试识别 四环素的灭活形式。我们还将对基因进行测序， 上游地区。虽然基因的表达不受 四环素，上游区域的缺失会影响 阻力来自序列的信息可能有助于解决 这一区域

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.