Binding and activation of host plasminogen on the surface of Francisella tularensis.
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.
Clinton
Shawn R
SR
Department of Molecular Sciences, The University of Tennessee Health Science Center, 858 Madison Avenue, Memphis, Tennessee 38163, USA.
Bina
James E
JE
Hatch
Thomas P
TP
Whitt
Michael A
MA
Miller
Mark A
MA
D000614:Aminocaproates / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism*; D026481:Blotting, Far-Western; D004797:Enzyme-Linked Immunosorbent Assay; D005341:Fibrinolysin / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005604:Francisella tularensis / Q000378:metabolism* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D014406:Tularemia / Q000097:blood / Q000382:microbiology; D014774:Virulence
D000614:Aminocaproates; D001426:Bacterial Proteins; D005353:Fibronectins; D008565:Membrane Proteins; D010958:Plasminogen; D005341:Fibrinolysin