Antibiotic Resistance Transfer in Oral Anaerobes

描述(由申请人提供)：细菌之间的DNA转移被认为在抗生素耐药性的传播中起着重要作用。不幸的是，关于在自然细菌种群中发生的遗传转移的程度的信息很少。菌斑生物膜为研究易于获取的多物种种群中的遗传转移机制提供了一个极好的机会。种间遗传交换可能涉及抗生素耐药基因和其他毒力因子的共生水平转移，这可能有助于牙周感染对治疗的耐药性的发展。此外，口腔菌群的成员有可能将抗生素耐药性转移给其他病原体，这些病原体是口腔的短暂定居者。口腔细菌水平基因转移的基础分子研究具有重要意义。这项提案将概述启动口腔厌氧菌、卟啉单胞菌和普雷沃特氏菌成员中存在的四环素编码的共生转座子的分子研究的实验。这项建议的具体目标是：1)从临床分离株中“捕获”结合元件，并通过RFLP分析和接合分析比较它们的结构和行为；2)提交一个具有代表性的元件用于DNA测序，并使用得到的信息来根据基因含量和功能行为开发这些元件的分类系统。这些研究将为人类口腔菌群中水平转移元素的分布和功能提供重要的见解。

DESCRIPTION (provided by applicant): The transfer of DNA between bacterial species is assumed to play an important role in the dissemination of antibiotic resistance. Unfortunately, little information is available on the extent of genetic transfer occurring in natural bacterial populations. Plaque biofilms offer an excellent opportunity to study genetic transfer mechanisms in an easily accessed multi-species population. Interspecies genetic exchange can involve the conjugal horizontal transfer of antibiotic resistance genes and other virulence factors, which may contribute to the development of periodontal infections resistant to therapy. Additionally, members of the oral flora have the potential to transfer antibiotic resistance to other pathogens that are transient colonizers of the mouth. There is a significant need for basic molecular studies into horizontal gene transfer in oral bacteria. This proposal will outline experiments to initiate molecular studies of the tetQ-encoding conjugal transposons present in members of the oral anaerobes Porphyromonas and Prevotella. The Specific Aims of this proposal are 1) to "capture" conjugative elements from clinical isolates and compare their structure and behavior through RFLP analysis and conjugation assays, and 2) to submit a representative element for DNA sequencing, and use the resulting information to develop a classification system for these elements, based on gene content and functional behavior. These studies will provide important insights into the distribution and functionality of horizontally transferred elements in the human oral flora.