ANTIBIOTIC RESISTANCE IN ORAL & COLONIC ANAEROBES

在专性厌氧菌中，拟杆菌占有突出的地位 在人类口腔和肠道的微生物生态学中。 虽然通常是本土的，但口腔来源的拟杆菌往往是 与牙周病性牙菌斑有关。 一种肠道种属，B。 fragilis是最常见的从软组织中分离的厌氧微生物 感染. 对克林霉素的抗药性的出现 (Ccr)，以及其他抗生素可能会影响对 类杆菌感染。 虽然抗性表型已被追溯到 质粒，许多菌株具有可转移的抗性元件， 与质粒DNA无关。 在这个应用程序中，我们将测试 假设一个B. fragilis质粒pBF 4是一种 转座子 这些研究将涉及末端的碱基序列分析 这种假定的转座子和基因测试的能力， 串联换位 主要工作将是确定 拟杆菌中非质粒相关Ccr的遗传基础。 使用 物理和遗传的方法，我们将测试的假设，一个这样的 元件占据染色体整合位点。 我们亦会探讨 在口腔类杆菌中存在耐药传递元件的可能性， 我们将评估它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遗传 方法学，包括突变体分离、传递遗传学、分子生物学 克隆、原位杂交和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.