Binding and activation of host plasminogen on the surface of Francisella tularensis

Shawn R. Clinton, James E. Bina, Thomas P. Hatch, Michael Whitt, Mark Miller

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background. Francisella tularensis (FT) is a gram-negative facultative intracellular coccobacillus and is the causal agent of a life-threatening zoonotic disease known as tularemia. Although FT preferentially infects phagocytic cells of the host, recent evidence suggests that a significant number of bacteria can be found extracellularly in the plasma fraction of the blood during active infection. This observation suggests that the interaction between FT and host plasma components may play an important role in survival and dissemination of the bacterium during the course of infection. Plasminogen (PLG) is a protein zymogen that is found in abundance in the blood of mammalian hosts. A number of both gram-positive and gram-negative bacterial pathogens have the ability to bind to PLG, giving them a survival advantage by increasing their ability to penetrate extracellular matrices and cross tissue barriers. Results. We show that PLG binds to the surface of FT and that surface-bound PLG can be activated to plasmin in the presence of tissue PLG activator in vitro. In addition, using Far-Western blotting assays coupled with proteomic analyses of FT outer membrane preparations, we have identified several putative PLG-binding proteins of FT. Conclusions. The ability of FT to acquire surface bound PLG that can be activated on its surface may be an important virulence mechanism that results in an increase in initial infectivity, survival, and/or dissemination of this bacterium in vivo.

Original languageEnglish (US)
Article number76
JournalBMC Microbiology
Volume10
DOIs
StatePublished - Apr 5 2010

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Francisella tularensis
Plasminogen
Bacteria
Far-Western Blotting
Tularemia
Enzyme Precursors
Fibrinolysin
Zoonoses
Tissue Plasminogen Activator
Phagocytes
Infection
Proteomics
Extracellular Matrix
Virulence
Carrier Proteins
Membranes

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Microbiology (medical)

Cite this

Binding and activation of host plasminogen on the surface of Francisella tularensis. / Clinton, Shawn R.; Bina, James E.; Hatch, Thomas P.; Whitt, Michael; Miller, Mark.

In: BMC Microbiology, Vol. 10, 76, 05.04.2010.

Research output: Contribution to journalArticle

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abstract = "Background. Francisella tularensis (FT) is a gram-negative facultative intracellular coccobacillus and is the causal agent of a life-threatening zoonotic disease known as tularemia. Although FT preferentially infects phagocytic cells of the host, recent evidence suggests that a significant number of bacteria can be found extracellularly in the plasma fraction of the blood during active infection. This observation suggests that the interaction between FT and host plasma components may play an important role in survival and dissemination of the bacterium during the course of infection. Plasminogen (PLG) is a protein zymogen that is found in abundance in the blood of mammalian hosts. A number of both gram-positive and gram-negative bacterial pathogens have the ability to bind to PLG, giving them a survival advantage by increasing their ability to penetrate extracellular matrices and cross tissue barriers. Results. We show that PLG binds to the surface of FT and that surface-bound PLG can be activated to plasmin in the presence of tissue PLG activator in vitro. In addition, using Far-Western blotting assays coupled with proteomic analyses of FT outer membrane preparations, we have identified several putative PLG-binding proteins of FT. Conclusions. The ability of FT to acquire surface bound PLG that can be activated on its surface may be an important virulence mechanism that results in an increase in initial infectivity, survival, and/or dissemination of this bacterium in vivo.",
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