Tilley Derek, Law Robert, Warren Sarah, Samis John A, Kumar Ayush
Centennial College, School of Engineering Technology and Applied Science, Toronto, ON, Canada; CancerControl, Alberta Health Services, Richmond Road Diagnostic & Treatment Centre, Calgary, AB, Canada.
FEMS Microbiol Lett. 2014 Jul;356(1):53-61. doi: 10.1111/1574-6968.12496. Epub 2014 Jun 23.
Acinetobacter baumannii is an important nosocomial pathogen that displays high antibiotic resistance. It causes a variety of infections including pneumonias and sepsis which may result in disseminated intravascular coagulation. In this work, we identify and characterize a novel secreted, zinc-dependent, metallo-endopeptidase CpaA (coagulation targeting metallo-endopeptidase of Acinetobacter baumannii) which deregulates human blood coagulation in vitro and thus is likely to contribute to A. baumannii virulence. Three quarters of the clinical isolates tested (n = 16) had the cpaA gene; however, it was absent from two type strains, A. baumannii ATCC 17978 and A. baumannii ATCC 19606. The CpaA protein was purified from one clinical isolate and was able to cleave purified factor (F) V and fibrinogen and reduce the coagulation activity of FV in human plasma. CpaA-treated plasma showed reduced clotting activity in contact pathway-activated partial thromboplastin time (aPTT) assays, but increased clotting activity in tissue factor pathway prothrombin time (PT) assays. A significant portion of clinically relevant A. baumannii isolates secrete a protease which targets and deregulates the coagulation system.
鲍曼不动杆菌是一种重要的医院病原体，具有高度的抗生素耐药性。它会引发多种感染，包括肺炎和败血症，这些感染可能导致弥散性血管内凝血。在这项研究中，我们鉴定并表征了一种新型的分泌型、锌依赖性金属内肽酶CpaA（鲍曼不动杆菌凝血靶向金属内肽酶），该酶在体外可破坏人体血液凝固，因此可能对鲍曼不动杆菌的毒力有影响。四分之三的测试临床分离株（n = 16）含有cpaA基因；然而，两种模式菌株，鲍曼不动杆菌ATCC 17978和鲍曼不动杆菌ATCC 19606中没有该基因。从一株临床分离株中纯化出CpaA蛋白，它能够切割纯化的因子（F）V和纤维蛋白原，并降低人血浆中FV的凝血活性。经CpaA处理的血浆在接触途径激活的部分凝血活酶时间（aPTT）测定中显示凝血活性降低，但在组织因子途径凝血酶原时间（PT）测定中凝血活性增加。很大一部分临床相关的鲍曼不动杆菌分离株分泌一种靶向并破坏凝血系统的蛋白酶。
