Université de Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.
Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Biomolecules. 2020 Nov 14;10(11):1554. doi: 10.3390/biom10111554.
The Gram-negative bacterium causes plague, a fatal flea-borne anthropozoonosis, which can progress to aerosol-transmitted pneumonia. overcomes the innate immunity of its host thanks to many pathogenicity factors, including plasminogen activator, Pla. This factor is a broad-spectrum outer membrane protease also acting as adhesin and invasin. uses Pla adhesion and proteolytic capacity to manipulate the fibrinolytic cascade and immune system to produce bacteremia necessary for pathogen transmission via fleabite or aerosols. Because of microevolution, invasiveness has increased significantly after a single amino-acid substitution (I259T) in Pla of one of the oldest phylogenetic groups. This mutation caused a better ability to activate plasminogen. In paradox with its fibrinolytic activity, Pla cleaves and inactivates the tissue factor pathway inhibitor (TFPI), a key inhibitor of the coagulation cascade. This function in the plague remains enigmatic. Pla (or ) had been used as a specific marker of , but its solitary detection is no longer valid as this gene is present in other species of . Though recovering hosts generate anti-Pla antibodies, Pla is not a good subunit vaccine. However, its deletion increases the safety of attenuated strains, providing a means to generate a safe live plague vaccine.
革兰氏阴性菌 引起鼠疫，这是一种致命的跳蚤传播人畜共患病，可发展为气溶胶传播性肺炎。 克服了其宿主的先天免疫，这要归功于许多致病因子，包括纤溶酶原激活物 Pla。该因子是一种广谱的外膜蛋白酶，也具有黏附素和侵袭素的作用。 通过 Pla 的黏附和蛋白水解能力， 操纵纤维蛋白溶解级联和免疫系统，产生通过跳蚤叮咬或气溶胶传播病原体所必需的菌血症。由于微观进化， 在一个古老的 系统发育群的 Pla 中的一个单一氨基酸取代（I259T）之后，侵袭性显著增加。这种突变导致更好地激活纤溶酶原的能力。与它的纤维蛋白溶解活性相反，Pla 裂解并失活组织因子途径抑制剂（TFPI），这是凝血级联的关键抑制剂。这种在鼠疫中的功能仍然是个谜。 Pla（或 ）曾被用作 的特异性标志物，但由于该基因存在于其他 物种中，因此其单独检测不再有效。尽管恢复宿主会产生抗 Pla 抗体，但 Pla 不是一种良好的亚单位疫苗。然而，其缺失增加了减毒 菌株的安全性，为生成安全的活鼠疫疫苗提供了一种手段。
