Phase variable control of Acinetobacter baumannii virulence

 描述(申请人提供)：革兰氏阴性杆菌鲍曼不动杆菌是人类医院感染的主要原因。鲍曼不动杆菌菌株的出现，使这些感染的治疗变得极其困难。这凸显了找到抗击这些感染的新方法的重要性。这一建议解决了鲍曼不动杆菌的一个阶段变量机制，该机制控制多种表型，包括菌落不透明、群体感应和毒力。利用等位基因替换和全基因组测序相结合的方法，将确定导致这一阶段变化的机制。阶段变化对全球基因表达的影响也将使用RNA-Seq来确定。最终，了解控制这一阶段变异的分子机制以及这种变异影响的整体表型将为调节鲍曼不动杆菌的毒力提供重要信息。

 DESCRIPTION (provided by applicant): The Gram-negative bacterium Acinetobacter baumannii is a leading cause of nosocomial infections in humans. The emergence of A. baumannii strains resistant to most, and in some cases, all available antibiotics has made the treatment of these infections exceedingly difficult. This underlies the importance of finding new ways to combat these infections. This proposal addresses a phase variable mechanism in A. baumannii that controls multiple phenotypes, including colony opacity, quorum sensing and virulence. Using a combination of allelic replacement and whole genome sequencing, the mechanism responsible for this phase variation will be determined. The impact of phase variation on global gene expression will also be determined using RNA- Seq. Ultimately, an understanding of the molecular mechanisms that control this phase variation and the overall phenotypes impacted by this variation will provide important information on the regulation of virulence in A. baumannii.