<i>Yersinia pestis</i> Plasminogen Activator
The Gram-negative bacterium <i>Yersinia pestis</i> causes plague, a fatal flea-borne anthropozoonosis, which can progress to aerosol-transmitted pneumonia. <i>Y. pestis</i> overcomes the innate immunity of its host thanks to many pathogenicity factors, including plasminogen a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/11/1554 |
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| author | Florent Sebbane Vladimir N. Uversky Andrey P. Anisimov |
| author_facet | Florent Sebbane Vladimir N. Uversky Andrey P. Anisimov |
| author_sort | Florent Sebbane |
| collection | DOAJ |
| description | The Gram-negative bacterium <i>Yersinia pestis</i> causes plague, a fatal flea-borne anthropozoonosis, which can progress to aerosol-transmitted pneumonia. <i>Y. pestis</i> 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. <i>Y. pestis</i> 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, <i>Y. pestis</i> invasiveness has increased significantly after a single amino-acid substitution (I259T) in Pla of one of the oldest <i>Y. pestis</i> 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 <i>pla</i>) had been used as a specific marker of <i>Y. pestis</i>, but its solitary detection is no longer valid as this gene is present in other species of <i>Enterobacteriaceae</i>. Though recovering hosts generate anti-Pla antibodies, Pla is not a good subunit vaccine. However, its deletion increases the safety of attenuated <i>Y. pestis</i> strains, providing a means to generate a safe live plague vaccine. |
| first_indexed | 2024-03-10T14:50:31Z |
| format | Article |
| id | doaj.art-30833d7deaf04767bc3315d45ed2dcae |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T14:50:31Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-30833d7deaf04767bc3315d45ed2dcae2023-11-20T20:59:41ZengMDPI AGBiomolecules2218-273X2020-11-011011155410.3390/biom10111554<i>Yersinia pestis</i> Plasminogen ActivatorFlorent Sebbane0Vladimir N. Uversky1Andrey P. Anisimov2Université de Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019—UMR9017—CIIL—Center for Infection and Immunity of Lille, F-59000 Lille, FranceDepartment of Molecular Medicine and USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USALaboratory for Plague Microbiology, State Research Center for Applied Microbiology and Biotechnology, Especially Dangerous Infections Department, 142279 Obolensk, Moscow Region, RussiaThe Gram-negative bacterium <i>Yersinia pestis</i> causes plague, a fatal flea-borne anthropozoonosis, which can progress to aerosol-transmitted pneumonia. <i>Y. pestis</i> 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. <i>Y. pestis</i> 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, <i>Y. pestis</i> invasiveness has increased significantly after a single amino-acid substitution (I259T) in Pla of one of the oldest <i>Y. pestis</i> 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 <i>pla</i>) had been used as a specific marker of <i>Y. pestis</i>, but its solitary detection is no longer valid as this gene is present in other species of <i>Enterobacteriaceae</i>. Though recovering hosts generate anti-Pla antibodies, Pla is not a good subunit vaccine. However, its deletion increases the safety of attenuated <i>Y. pestis</i> strains, providing a means to generate a safe live plague vaccine.https://www.mdpi.com/2218-273X/10/11/1554<i>Yersinia pestis</i>plasminogen activatoromptinpathogenicity factorpathogenesisplague |
| spellingShingle | Florent Sebbane Vladimir N. Uversky Andrey P. Anisimov <i>Yersinia pestis</i> Plasminogen Activator Biomolecules <i>Yersinia pestis</i> plasminogen activator omptin pathogenicity factor pathogenesis plague |
| title | <i>Yersinia pestis</i> Plasminogen Activator |
| title_full | <i>Yersinia pestis</i> Plasminogen Activator |
| title_fullStr | <i>Yersinia pestis</i> Plasminogen Activator |
| title_full_unstemmed | <i>Yersinia pestis</i> Plasminogen Activator |
| title_short | <i>Yersinia pestis</i> Plasminogen Activator |
| title_sort | i yersinia pestis i plasminogen activator |
| topic | <i>Yersinia pestis</i> plasminogen activator omptin pathogenicity factor pathogenesis plague |
| url | https://www.mdpi.com/2218-273X/10/11/1554 |
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