Acquisition of Host Plasmin Activity by the Swine PathogenStreptococcus suisSerotype 2

Abstract

In this study, the plasminogen-binding activity of Streptococcus suis serotype 2 was investigated. Bound human plasminogen was activated by purified streptokinase, urokinase, or Streptococcus dysgalactiae subsp. equisimilis culture supernatant. Both human and porcine plasminogen were bound by S. suis. Binding was inhibited by -aminocaproic acid, and the plasminogen receptor was heat and sodium dodecyl sulfate resistant. One of the receptors was identified as glyceraldehyde-3-phosphate dehydrogenase. S. suis-associated plasmin activity was capable of activating free plasminogen, which in turn could contribute to degradation of fibronectin. This is the first report on the plasminogen-binding activity of S. suis. Further studies may reveal a contribution of this activity to the virulence of S. suis.Streptococcus suis, an important swine pathogen worldwide, is made up of 35 serotypes (1 to 34 and 1/2) (12). Although all serotypes can cause infections, serotype 2 is the most prevalent one isolated from diseased pigs (9, 11). Septicemia, arthritis, meningitis, and sudden death are the most important clinical signs associated with S. suis infections (11). Cases of meningitis and endocarditis caused by S. suis have also been reported in workers associated with the pig industry (11). Although several S. suis virulence factors have been identified and characterized, the exact mechanisms by which this bacterium invades the host and causes infections are still unclear. The only factor considered essential for the pathogenicity of S. suis is the polysaccharide capsule (3). An important feature, which could play an important role in the pathogenicity of S. suis, is its ability to bind host proteins, which may camouflage it and thus protect it from the host immune system. Fibronectin (7), albumin (21), and immunoglobulin G (1, 23) receptors have been identified on the cell surface of S. suis and have been proposed as virulence factors.Plasminogen is a 92-kDa protein that is an important component of the fibrinolytic system. Its activation into plasmin, a serine protease, is tightly regulated by the equilibrium between plasmin activators (urokinase plasmin activator [u-PA] as well as tissue plasminogen activator) and inhibitors (␣2-antiplasmin and ␣2-macroglobulin) (15). Plasminogen can also be activated by microbial products including streptokinase and staphylokinase produced by group A streptococci and Staphylococcus aureus, respectively (15). Many group A and C streptococci bind plasminogen on their cell surfaces (15). In a number of cases, the receptors have been characterized and identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or ␣-enolase (17,19,20,24). The plasmin activity generated on the bacterial cell surface is protected from host inhibitors and can activate latent u-PA and tissue plasminogen activator, which subsequently activate plasminogen (15). This mechanism of acquisition of a host proteinase activity increases the invasive potential of some pathogens, including Streptococcus pneumoniae (8). The ...

Isolation and characterization of α-enolase, a novel fibronectin-binding protein from Streptococcus suis

“…Fischetti, 1998;Pancholi, 2001). In this study we confirmed that, in addition to a previously described GAPDH (Jobin et al, 2004), SsEno is also an S. suis plasminogen-binding protein. Although it has been demonstrated recently that enolases of other Gram-positive bacteria bind to laminin and/or collagen (Antikainen et al, 2007), we could not identify any adhesion activity of rSsEno to either of these two proteins (M. Esgleas and others, unpublished observations).…”

“…The role of FBPS in bacterial pathogenesis is not well understood. However, studies with the fbps mutant suggest that this protein could play a role in S. suis colonization of various organs (de Greeff et al, 2002).Another S. suis adhesin that is able to bind to different host proteins such as plasminogen and albumin is the 39 kDa glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (Jobin et al, 2004;Quessy et al, 1997). Evidence that this protein is involved in the binding of S. suis to host tissues has been provided by the finding that mutants deficient in the surface expression of GAPDH have decreased binding to tracheal cells and porcine tracheal rings (Brassard et al, 2001.…”

Interaction with human plasminogen system turns on proteolytic activity in Streptococcus agalactiae and enhances its virulence in a mouse model

“…GAPDH has also been described as a plasminogen receptor in Streptococcus suis [25] and as a surface-displayed plasminogen-binding protein in Streptococcus pneumoniae [26]. Recently, Boel et al constructed a GAS mutant unable to secrete GAPDH, the enzyme being retained in the cytoplasm and/or in the membrane [27].…”

Streptococcus pneumoniae enolase is important for plasminogen binding despite low abundance of enolase protein on the bacterial cell surface

“…Among the plasminogen-binding proteins in Gram-positive bacteria are glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and enolase, important glycolytic enzymes generally found in the cytosolic compartment (for review, see Pancholi & Chhatwal, 2003). Although these enzymes lack signal sequences and typical motifs for membrane anchoring, independent groups have shown the proteins to be surface-exposed on Streptococcus agalactiae (Hughes et al, 2002), Streptococcus mutans (Ge et al, 2004), Streptococcus pneumoniae (Bergmann et al, 2001(Bergmann et al, , 2004bWhiting et al, 2002), Streptococcus pyogenes (D 'Costa et al, 2000;Pancholi & Fischetti, 1992, 1998 and Streptococcus suis (Jobin et al, 2004) by immunochemical and/or immunoelectron microscopic methods.…”