ANTIBIOTIC RESISTANCE IN ORAL AND COLONIC ANAEROBES

类杆菌是专性厌氧菌的一种，占据了突出的地位 在人类口腔和肠道的微生物生态中。 虽然通常是土生土长的，但口腔起源的类杆菌通常 与牙周病牙菌斑有关。其中一种为B。 脆弱菌是软组织中最常见的厌氧菌 感染。出现对首选药物克林霉素的抗药性 (Ccr)，以及其他可能危及治疗的抗生素 类杆菌感染。尽管耐药表型已经被追溯到 许多菌株具有可转移的抗性元件，这些元件是 与质粒DNA无关。在本应用程序中，我们将测试 假设脆弱芽孢杆菌质粒pBF4的CCR决定簇是一个 转座子。这些研究将涉及末端的碱基序列分析 这个假定的转座子和它的能力的基因测试 连续换位。主要工作将集中在定义 类杆菌非质粒相关CCR的遗传学基础。vbl.使用 物理和遗传方法，我们将测试这样一个假设 该元件占据了染色体整合部位。我们还将探讨 口腔类杆菌和类杆菌中存在耐药转移元件的可能性 我们将评估他们交换抗性决定因素的能力 肠道物种。这项工作将使用广泛的现代基因 方法学包括突变分离、传递遗传学、分子生物学 克隆、原位滤膜杂交和DNA碱基序列分析。

Species of the obligate anaerobe, Bacteroides occupy a prominent position in the microbial ecology of the human oral cavity and intestinal tract. Although normally indigenous, Bacteroides of oral origin are often associated with periodontopathic dental plaque. One intestinal species, B. fragilis, is the most commonly isolated anaerobic organism from soft-tissue infections. The emergence of resistance to the drug of choice, clindamycin (Ccr), and to other antibiotics threatens to compromise the treatment of Bacteroides infections. Although resistance phenotypes have been traced to plasmids, many strains possess transferable resistance elements that are not associated with plasmid DNA. In this application we shall test the hypothesis that the Ccr determinant of a B. fragilis plasmid, pBF4, is a transposon. These studies will involve base sequence analysis of the ends of this putative transposon and genetic tests of its ability to undergo serial transposition. Major effort will be directed towards defining the genetic basis of the non-plasmid associated Ccr in Bacteroides. Using physical and genetic approaches we shall test the hypothesis that one such element occupies a chromosomal integration site. We shall also explore the possibility that resistance transfer elements occur in oral Bacteroides and we shall assess their ability to exchange resistance determinants with intestinal species. This work will use a wide array of modern genetic methodology including mutant isolation, transmission genetics, molecular cloning, in situ filter blot hybridization and DNA base sequence analysis.