BIOLOGY OF PCRV

院内肺炎是第二常见的院内感染 以及院内感染死亡的首要原因。P. 铜绿假单胞菌是医院内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 尽管接受了适当的抗生素治疗，死亡率仍高达60%。也是 慢性感染铜绿假单胞菌的患者(即：囊性 纤维化、艾滋病毒患者和支气管扩张患者)对 抗生素，并可能死于感染。因此，迫切需要 用于治疗铜绿假单胞菌感染的新方法。的长期目标 这项拨款是为了确定一种假单胞蛋白PcrV的细胞生物学。 PcrV是细菌III型分泌系统的一部分；PcrV参与 铜绿假单胞菌将细菌毒素转移到真核细胞中。它 也与Yersinia的一种蛋白质LcrV高度同源，LcrV也参与了 易位。这种细菌的毒素进入真核细胞。抗病毒抗体 LCRV可以保护动物免受鼠疫杆菌和其他耶尔森氏菌的感染 菌株。然而，尽管LcrV和PcrV之间有相似之处，但有 此外，与PcrV相比，LcrV在 这两个菌株的毒素分泌调节。因此，PcrV认股权证 独立调查。这个小组已经表明，PcrV可以访问 抗体中和，抗体附着在PcrV上阻止 假单胞菌毒素在真核细胞中的移位及其抗体 PcrV可保护感染毒力铜绿假单胞菌的动物免受肺损伤， 败血症和死亡。因此，针对PcrV的治疗方法出现在临床上。 很有用。最后，许多致命的革兰氏阴性细菌利用III型 将细菌毒素送入真核细胞的分泌系统。这些 革兰氏阴性菌，包括肠道致病性大肠杆菌、耶尔森氏菌、沙门氏菌、 产生的细菌蛋白质和结构与在 铜绿假单胞菌。因此，理解PcrV的作用机制 细菌易位到真核细胞可能有助于发展 针对这种广泛存在的革兰氏阴性细菌分泌物的其他治疗方法 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.