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Advances in Yersinia Research pp 253–260Cite as

Substrates of the Plasminogen Activator Protease of Yersinia pestis

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 954))

Abstract

The plasminogen activator protease (Pla) of Yersinia pestis is a critical virulence determinant in the progression of both bubonic and pneumonic plague. A member of the omptin family of Gram-negative transmembrane proteases, Pla forms a conserved β-barrel fold in the bacterial outer membrane which permits the interaction of the protease with target substrates for cleavage. In vitro studies have identified numerous mammalian host targets, many of which comprise components of the coagulation and fibrinolytic cascades. Through the cleavage of host plasminogen, α2-antiplasmin, plasminogen activator inhibitor-1 (PAI-1), thrombin-activatable fibrinolysis inhibitor, and tissue factor pathway inhibitor, Pla is hypothesized to disrupt coagulation pathways that are initiated as a natural host response to infection and inflammation. The clearance of fibrin clots, enhanced by the activities of Pla, may alleviate physical barriers to bacterial dissemination and inhibit the recruitment of immune cells. Subversion of innate immunity may be further potentiated through the Pla-dependent inactivation of complement protein C3 and cationic antimicrobial peptides. Currently, the precise molecular mechanisms of Pla-conferred virulence in vivo remain unclear and likely vary based upon route of infection. However, evidence supports Pla as a versatile virulence factor that may specifically cleave unique subsets of host proteins during the progression of bubonic and pneumonic plague.

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Acknowledgments

The authors thank Dr. Jay Degen for helpful discussions. This work was supported by NIH/NIAID grant R01 AI093727 to WWL. AJC was supported by NIH/NIAID grant T32 AI007476.

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Authors and Affiliations

  1. Department of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA

    Adam J. Caulfield & Wyndham W. Lathem

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  1. Adam J. Caulfield
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  2. Wyndham W. Lathem
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Correspondence to Wyndham W. Lathem .

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  1. , Centro de Pesquisa Aggeu Magalhães, Campus da UFPE, Recife, 50670, Brazil

    Alzira Maria Paiva de Almeida

  2. , Centro de Pesquisa Aggeu Magalhães, Campus da UFPE, Recife, 50670-420, Brazil

    Nilma Cintra Leal

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Caulfield, A.J., Lathem, W.W. (2012). Substrates of the Plasminogen Activator Protease of Yersinia pestis . In: de Almeida, A., Leal, N. (eds) Advances in Yersinia Research. Advances in Experimental Medicine and Biology, vol 954. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3561-7_32

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