BIOLOGY OF PCRV

医院获得性肺炎是第二常见的医院感染 也是医院感染死亡的主要原因。P. 铜绿假单胞菌是医院感染中最常见的革兰氏阴性菌， 肺炎和与铜绿假单胞菌感染相关的医院内肺炎 尽管进行了适当的抗生素治疗，死亡率仍高达60%。也 慢性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）变得对 抗生素，并可能死于他们的感染。因此，迫切需要 用于铜绿假单胞菌感染的新型治疗。的长期目标 该基金将用于确定假单胞菌蛋白PcrV的细胞生物学。 PcrV是细菌III型分泌系统的一部分; 铜绿假单胞菌将细菌毒素转运到真核细胞中。它 也与LcrV高度同源，LcrV是一种耶尔森氏菌蛋白，也参与了 易位将细菌毒素导入真核细胞。抗体 LcrV可以保护动物免受Y.鼠疫和其他耶尔森氏菌 菌株然而，尽管LcrV和PcrV之间存在相似之处， LcrV与PcrV在肿瘤中的作用也存在重要差异。 调节两种菌株的毒素分泌。因此，PcrV保证 独立调查。该小组已经表明，PcrV是可访问的， 抗体中和，即抗体与PcrV的连接阻断了 假单胞菌毒素易位到真核细胞中， PcrV保护感染有毒性铜绿假单胞菌的动物免受肺损伤， 败血症和死亡因此，靶向PcrV的治疗出现在临床上 有用的.最后，许多毒性革兰氏阴性细菌利用III型 将细菌毒素递送到真核细胞中的分泌系统。这些 革兰氏阴性菌，包括肠病性E.大肠杆菌，耶尔森氏菌，沙门氏菌， 产生的细菌蛋白质和结构类似于 P.aeruginosa.因此，了解PcrV在 细菌易位到真核细胞中可能有助于 其它针对这种广泛存在的革兰氏阴性细菌分泌的疗法 系统

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.