Enolases from Gram-positive bacterial pathogens and commensal lactobacilli share functional similarity in virulence-associated traits

Abstract

Enolase occurs as a cytoplasmic and a surface-associated protein in bacteria. Enolases of the bacterial pathogens Streptococcus pyogenes, Streptococcus pneumoniae and Staphylococcus aureus, as well as of the commensal lactic acid bacteria, Lactobacillus crispatus and Lactobacillus johnsonii, were purified as His(6)-fusion proteins from recombinant Escherichia coli. The fusion proteins were compared for putative virulence-associated functions, i.e., binding of human plasminogen, enhancement of plasminogen activation by human plasminogen activators, as well as binding to immobilized laminin, fibronectin and collagens. The individual enolases showed varying efficiencies in these functions. In particular, highly and equally effective interactions with plasminogen and laminin were seen with lactobacillar and staphylococcal enolases.

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

“…Both ELISA and SPR also demonstrated, as described for other pathogens, that the interaction between rSsEno and plasminogen is specific, suggesting that this interaction is also a biologically significant event. This provides further evidence to support the earlier finding that bacterial enolases interact with plasminogen with high affinity (Antikainen et al, 2007;Kinnby et al, 2008). In fact, the low nanomolar affinity constant between SsEno and plasminogen obtained in this study agrees with values obtained for the adhesion to plasminogen of enolases from S. pyogenes (Pancholi & Fischetti, 1998) and S. pneumoniae (Bergmann et al, 2003).…”

“…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2007), we could not identify any adhesion activity of rSsEno to either of these two proteins (M. Esgleas and others, unpublished observations). Interestingly, in addition to the fibronectin and plasminogen-binding activities of the rSsEno, a heat-shock protein activity [as described previously for other enolases (Iida & Yahara, 1985;Prasad et al, 2003)] and an IgGbinding property of this protein have also been observed (M. Esgleas and others, unpublished observations).…”

“…These results were confirmed using rSsEno cloned and expressed in the present study. In fact, Antikainen et al (2007) have recently reported that a-enolases from other Gram-positive bacteria, such as S. pyogenes, Streptococcus pneumoniae, Staphylococcus aureus, Lactobacillus crispatus and Lactobacillus johnsonii, do not possess the ability to bind to fibronectin. Thus, the interaction of enolase with fibronectin may serve different purposes in S. suis from those in the pathogenic and commensal bacteria studied in that work.…”

“…As a consequence of plasminogen activation on bacterial surfaces, bacteria become armed with the broad-substrate-spectrum proteolytic potential of plasmin that is not susceptible to regulation by host-derived inhibitors (Lottenberg et al, 1994). The capture of plasminogen by adhesins such as SsEno and GAPDH and its conversion to plasmin has been described for other pathogens (Antikainen et al, 2007;Kinnby et al, 2008) and can be used to facilitate bacterial penetration through biological membranes such as the blood-brain barrier, and therefore could represent an important determinant of virulence. The role of SsEno in studies using endothelial-cell monolayers in a trans-well system is currently under investigation in our laboratory.…”

Dihydrolipoamide Dehydrogenase of Pseudomonas aeruginosa Is a Surface-Exposed Immune Evasion Protein That Binds Three Members of the Factor H Family and Plasminogen

“…When activated by endogenous activators like tissue-type plasminogen activator or urokinasetype plasminogen activator (uPA), the protease plasmin degrades ECM components like fibrinogen, fibronectin, vitronectin, and laminin and regulates cell migration, coagulation, fibrinolysis, inflammation, wound healing, and tissue remodeling (18,19). Plasminogen is acquired by several pathogens, including P. aeruginosa, Streptococcus pneumoniae, Borrelia burgdorferi, Staphylococcus aureus, Lactobacillus johnsonii, and Candida albicans for ECM interaction, and activated plasmin is then used for destruction of host basement membranes and ECM (11,(20)(21)(22)(23).…”