Phages of Burkholderia Cepacia: Biology and Therapeutics

描述(申请人提供)：在过去的20年里，洋葱伯克霍尔德氏菌复合体(BCC)的细菌已经成为囊性纤维症患者的重要机会性病原体。感染基底细胞癌的患者表现出不可预测和多变的临床过程，高达25%的患者发展为致命的坏死性肺炎。大多数BCC菌株的广谱抗药性严重限制了治疗选择，感染通常不可能根除。因此，迫切需要新的策略来治疗囊性纤维化患者的基底细胞癌感染。噬菌体(专门检测和杀死细菌的病毒)提供了现代生物学时代尚未开发的抗菌活性来源。主要使用土壤作为来源，我们已经开始组装和鉴定一个针对BCC菌株的毒力“杀手噬菌体”文库。我们建议在小鼠肺部感染模型和呼吸道上皮细胞培养模型中测试噬菌体的治疗效果。该项目将提供有关如何使用噬菌体治疗感染的洋葱芽孢杆菌感染的关键信息。 这项研究与公共卫生的相关性：细菌对抗生素的抗药性继续增加。必须用新的抗击感染战略来应对传染病治疗方面的这一巨大挑战。一种方法是对抗生素出现之前广泛使用的抗细菌感染方法的现代实施，涉及使用自然产生的“杀伤性噬菌体”，即能够摧毁抗药性细菌的细菌病毒。该项目旨在探索使用这些天然抗菌剂来满足这一关键的公共卫生需求。

DESCRIPTION (provided by applicant): During the past 20 years, bacteria of the Burkholderia cepacia complex (Bcc) have become an important opportunistic pathogen in persons with cystic fibrosis. Patients infected with Bcc exhibit an unpredictable and variable clinical course, with up to 25% developing fatal necrotizing pneumonia. The broad-spectrum antimicrobial resistance of most Bcc strains severely limits treatment options and infection is typically impossible to eradicate. Hence, new strategies are urgently needed to treat Bcc infection in cystic fibrosis patients. Bacteriophages (viruses that specifically detect and kill bacteria) provide a source of antimicrobial activity as yet unexploited in the era of modern biology. Primarily using soil as a source, we have begun assembling and characterizing a library of virulent "killer phages" against Bcc strains. We propose to test the therapeutic effect of phage in a murine lung infection model and an airway epithelial cell culture model. This project will provide critical information about how phage can be used to treat B. cepacia infection in infected individuals. Relevance of this research to public health: Resistance of bacteria to antibiotics continues to increase. This enormous challenge to the treatment of infectious diseases must be met with new strategies to combat infection. One approach, a modern implementation of what was widely used against bacterial infection before the onset of antibiotics, involves the use of naturally occurring 'killer phage", bacterial viruses that are capable of destroying drug-resistant bacteria. This project seeks to explore the use of these natural antibacterial agents to address this critical public health need.