Phages of Burkholderia cepacia:Biology and Therapeutics

洋葱伯克霍尔德菌噬菌体：生物学和治疗学

• 批准号: 7371145
• 负责人: RYLAND F YOUNG
• 金额: $ 31.68万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7371145
• 关键词: Address; Affinity; Anti-Bacterial Agents; Antibiotics; Antimicrobial Resistance; Bacteria; Bacterial Infections; Bacteriophages; Biochemistry; Biology; Burkholderia cepacia; Burkholderia cepacia complex; Clinical; Communicable Diseases; Cystic Fibrosis; Epithelial Cells; Exhibits; Genomics; Human; Individual; Infection; Libraries; Lung; Microbiology; Modeling; Molecular; Mus; Pathogenesis; Patients; Persons; Pneumonia; Prophylactic treatment; Public Health; Range; Research; Soil; Source; Surface; Technology; Testing; Therapeutic; Therapeutic Effect; Virulent; Virus; antimicrobial; bacterial resistance; base; cystic fibrosis patients; drug resistant bacteria; experience; infectious disease treatment; interest; killings; microbial; pathogen; receptor

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.

描述（由申请人提供）：在过去 20 年中，洋葱伯克霍尔德氏菌复合体 (Bcc) 细菌已成为囊性纤维化患者的重要机会致病菌。感染 Bcc 的患者表现出不可预测且多变的临床病程，高达 25% 的患者发展为致命性坏死性肺炎。大多数 Bcc 菌株的广谱抗菌药物耐药性严重限制了治疗选择，并且感染通常无法根除。因此，迫切需要新的策略来治疗囊性纤维化患者的 Bcc 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。我们主要使用土壤作为来源，开始组装和表征针对 Bcc 菌株的剧毒“杀手噬菌体”库。我们建议在小鼠肺部感染模型和气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受感染个体的洋葱伯克霍尔德杆菌感染的重要信息。 这项研究与公共卫生的相关性：细菌对抗生素的耐药性持续增加。必须采取新的策略来应对传染病治疗的这一巨大挑战。一种方法是在抗生素出现之前广泛用于对抗细菌感染的方法的现代实施，涉及使用天然存在的“杀手噬菌体”，即能够消灭耐药细菌的细菌病毒。该项目旨在探索使用天然存在的“杀手噬菌体”。这些天然抗菌剂可以满足这一关键的公共卫生需求。