BIOLOGY OF PCRV

PCRV 生物学

• 批准号: 6632180
• 负责人: Jeanine P Wiener-Kronish
• 金额: $ 31.46万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6632180
• 关键词: Pseudomonas aeruginosa; bacteria infection mechanism; bacterial antigens; bacterial toxins; bactericidal immunity; histopathology; immunologic assay /test; immunotherapy; laboratory mouse; nonhuman therapy evaluation; phagocytosis; protein localization; respiratory infections; tissue /cell culture

Nosocomial pneumonia is the second most common nosocomial infection and the leading cause of death from infection acquired in the hospital. P. aeruginosa is the most frequent gram negative bacteria involved in nosocomial pneumonia, and nosocomial pneumonias associated with P. aeruginosa infections have up to a 60% mortality despite appropriate antibiotic treatment. Also patients who are chronically infected with P. aeruginosa (i.e.: cystic fibrosis, HIV patients and bronchiectasis patients) become resistant to antibiotics and may die from their4 infections. Thus, there is an urgent need for novel treatments of P. aeruginosa infections. The long-term objectives of this grant are to determine the cell biology of a Pseudomonal protein, PcrV. PcrV is part of the bacterial type III secretory system; PcrV is involved in the translocation of bacterial toxins by P.aeruginosa into eukaryotic cells. It is also highly homologous to LcrV, a Yersinia protein also involved in the translocation. of that bacteria's toxins into eukaryotic cells. Antibodies to LcrV can protect animals from infections caused by Y. pestis and other Yersinia strains. Yet, although there are similarities between LcrV and PcrV, there are also important differences in the roles of LcrV compared to PcrV in the regulation of toxin secretion in the two strains. Therefore, PcrV warrants independent investigation. This group has shown that PcrV is accessible to antibody neutralization, that antibody attachment to PcrV blocks the translocation of the Pseudomonal toxins into eukaryotic cells and that antibody to PcrV protects animals infected with virulent P. aeruginosa from lung injury, sepsis and death. Therefore, therapies targeting PcrV appears clinically useful. Finally, many virulent gram negative bacteria utilize the type III secretory system which delivers bacterial toxins into eukaryotic cells. These gram negative bacteria, including enteropathic E. coli, Yersinia, Salmonella, produce bacterial proteins and structures similar to those found in P.aeruginosa. Therefore, understanding the mechanism of PcrV's role in bacterial translocation into eukaryotic cells may help in the development of other therapies targeting this widespread gram negative bacterial secretory system.

医院肺炎是第二大最常见的医院感染 以及在医院获得的感染死亡的主要原因。 P Aeruginosa是与医院有关的最常见的革兰氏阴性细菌 肺炎和与铜绿假单胞菌感染相关的肺炎 尽管有适当的抗生素治疗，但仍有60％的死亡率。还 长期感染铜绿假单胞菌的患者（即囊性 纤维化，HIV患者和支气管扩张患者）对 抗生素，可能死于40次感染。因此，迫切需要 用于铜绿假单胞菌感染的新治疗方法。长期目标 该赠款是为了确定假元蛋白PCRV的细胞生物学。 PCRV是细菌III型分泌系统的一部分； PCRV参与 p.aeruginosa将细菌毒素转移到真核细胞中。它 也与LCRV高度同源，Yersinia蛋白也参与 易位。该细菌的毒素进入真核细胞。抗体 LCRV可以保护动物免受柴和其他Yersinia引起的感染 菌株。然而，尽管LCRV和PCRV之间有相似之处 与PCRV相比，LCRV角色的重要差异也很重要 调节这两种菌株中的毒素分泌。因此，PCRV的认股权证 独立调查。该组表明PCRV可以访问 抗体中和，抗体附着PCRV会阻止 伪符号毒素转移到真核细胞中，该抗体 PCRV保护被毒性铜绿假单胞菌感染的动物免受肺损伤， 败血症和死亡。因此，靶向PCRV的疗法在临床上似乎是 有用。最后，许多有毒的革兰氏阴性细菌利用III型 分泌系统将细菌毒素传递到真核细胞中。这些 革兰氏阴性细菌，包括肠病大肠杆菌，耶尔森氏菌，沙门氏菌， 产生类似于在 P.Aeruginosa。因此，了解PCRV在 细菌易位到真核细胞可能有助于发展 其他针对这种广泛革兰氏阴性细菌分泌的疗法 系统。