Molecular cloning of an α-enolase from the human filarial parasite Onchocerca volvulus that binds human plasminogen

Jolodar, Abbas; Fischer, Peter; Bergmann, Simone; Büttner, Dietrich W.; Hammerschmidt, Sven; Brattig, Norbert W.

doi:10.1016/s0167-4781(03)00083-6

Cited by 108 publications

(67 citation statements)

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“…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).…”

Section: Discussionsupporting

confidence: 90%

“…Enolase has also been identified as a novel plasminogen receptor on the surface of many eukaryotic cells (Miles et al, 1991; Nakajima et al, 1994). This unexpected feature has also been described in several bacteria (such as Staphylococcus aureus and many streptococci), fungi and nematodes (Bergmann et al, 2001;Jolodar et al, 2003;Jong et al, 2003;Molkanen et al, 2002;Pancholi & Fischetti, 1998;Sharma et al, 2006). While the role of plasminogen as an important component in streptoccoci adhesion is well established (Pancholi et al, 2003), the role of enolase in bacterial adherence and host cell invasion has not, to our knowledge, been investigated previously.…”

mentioning

confidence: 68%

“…Electron microscopy corroborated this surface localization and also showed that SsEno is present at the surface in low abundance, a feature that has also been described for S. pneumoniae enolase (Kolberg et al, 2006). Moreover, such a relatively low amount has proven sufficient for contributing to bacterial pathogenesis (Bergmann et al, 2003). Interestingly, in addition to serotype 2, all reference strains of other serotypes of S. suis were found to express surface-exposed SsEno (M. Esgleas and others, unpublished observations).…”

Section: Discussionmentioning

confidence: 96%

“…Later, Bergmann et al (2003) identified another internal plasminogen-binding site in the pneumococcal enolase (FYDKERKVY) that is located on the outer surface of the octameric molecule (Ehinger et al, 2004), in which the lysines and glutamic acid are important for plasminogen binding (Bergmann et al, 2005). Importantly, SsEno possesses both plasminogen-binding motifs (M. Esgleas and others, unpublished observations), which could explain the similar nanomolar affinity constant of both S. pneumoniae (Bergmann et al, 2003) and S. suis enolase to plasminogen. Binding of plasminogen to S. suis enolase is inhibited by the lysine analogue EACA, which indicates involvement of lysine residues in this binding activity.…”

Section: Discussionmentioning

confidence: 98%

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

et al. 2008

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Streptococcus suis is an important swine pathogen that causes meningitis, endocarditis, arthritis and septicaemia. As a zoonotic agent, S. suis also causes similar diseases in humans. Binding of pathogenic bacteria to extracellular matrix components enhances their adhesion to and invasion of host cells. In the present study we isolated and identified a novel fibronectin-binding protein from S. suis. The native protein (designated SsEno) possessed not only high homology with other bacterial enolases but also enolase activity. We cloned, expressed and purified SsEno and showed that it is ubiquitously expressed by all S. suis serotypes and we identified its surface localization using immunoelectron microscopy. ELISA demonstrated that SsEno binds specifically to fibronectin and plasminogen in a lysine-dependent manner. Additional surface plasmon resonance assays demonstrated that SsEno binds to fibronectin or plasminogen with low nanomolar affinity. Inhibition experiments with anti-SsEno antibodies also showed that bacterial SsEno is important for the adhesion to and invasion of brain microvascular endothelial cells by S. suis. Overall, the present work is the first study, to our knowledge, to demonstrate a fibronectinbinding activity of a bacterial enolase, and shows that, similar to other bacterial fibronectin-binding proteins, SsEno may contribute to the virulence of S. suis. INTRODUCTIONStreptococcus suis is a major swine pathogen that causes septicaemia, meningitis, endocarditis and arthritis (Higgins & Gottschalk, 2005). Of the 35 known serotypes, serotype 2 is the most frequently isolated and associated with disease (Higgins & Gottschalk, 2005). It has been proposed that two serotypes (serotypes 32 and 34) be excluded from S. suis and redesignated Streptococcus orisratti (Hill et al., 2005). S. suis, especially serotype 2, has also been described as an important zoonotic agent that affects people in close contact with infected pigs or pork-derived products (Lun et al., 2007). Indeed, an important number of cases of human disease with a high rate of mortality in China were linked directly to a concurrent outbreak of S. suis infection in pigs (Ye et al., 2006).Little is known about S. suis virulence factors. The capsule polysaccharide (CPS) is a critical virulence factor, given that unencapsulated isogenic mutants are completely avirulent and rapidly cleared from the circulation in pig and mouse infection models (Charland et al., 2000;Smith et al., 1999). However, non-virulent strains are also encapsulated, indicating that the virulence of this pathogen is a multifactorial process . Other potential virulence factors have also been described in S. suis, including a haemolysin (suilysin), a 136 kDa muramidase-released protein (MRP), a 110 kDa extracellular factor (EF) protein, a hyaluronidase, a superoxide dismutase, various proteases, a serum opacity factor and different adhesins (Baums et al., 2006;.The pathogenesis of S. suis infection is not fully understood and likely involves many steps . Binding between b...

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Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 68%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 98%

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

et al. 2008

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“…It is largely unknown how glycolytic enzymes such as enolase lacking any signal peptide required for secretion and peptidoglycan-anchoring motifs are transported to and associated with bacterial surface structures or which factors influence this process. However, independent groups have shown the proteins to be surface exposed on S. pneumoniae (32,44), Streptococcus agalactiae (45), Streptococcus mutans (46), S. pyogenes (47,48), N. meningitidis (49), Listeria monocytogenes (50), C. albicans (51), Onchocerca volvulus (52), and eukaryotic cells (53,54) by immunochemical and/or immunoelectron microscopic methods. Several glycolytic enzymes and other typically cytoplasmic proteins, involved in metabolism, have been detected and assigned multiple functions on the surface of bacteria (50,(55)(56)(57).…”

Section: Figurementioning

confidence: 99%

Enolase ofStreptococcus pneumoniaeBinds Human Complement Inhibitor C4b-Binding Protein and Contributes to Complement Evasion

Agarwal

Hammerschmidt

Malm

et al. 2012

The Journal of Immunology

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Streptococcus pneumoniae (pneumococcus) is a pathogen that causes severe local and life-threatening invasive diseases, which are associated with high mortality rates. Pneumococci have evolved several strategies to evade the host immune system, including complement to disseminate and to survive in various host niches. Thus, pneumococci bind complement inhibitors such as C4b-binding protein (C4BP) and factor H via pneumococcal surface protein C, thereby inhibiting the classical and alternative complement pathways. In this study, we identified the pneumococcal glycolytic enzyme enolase, a nonclassical cell surface and plasminogen-binding protein, as an additional pneumococcal C4BP-binding protein. Furthermore, we demonstrated that human, but not mouse, C4BP bound pneumococci. Recombinant enolase bound in a dose-dependent manner C4BP purified from plasma, and the interaction was reduced by increasing ionic strength. Enolase recruited C4BP and plasminogen, but not factor H, from human serum. Moreover, C4BP and plasminogen bound to different domains of enolase as they did not compete for the interaction with enolase. In direct binding assays with recombinant C4BP mutants lacking individual domains, two binding sites for enolase were identified on the complement control protein (CCP) domain 1/CCP2 and CCP8 of the C4BP α-chains. C4BP bound to the enolase retained its cofactor activity as determined by C4b degradation. Furthermore, in the presence of exogenously added enolase, an increased C4BP binding to and subsequently decreased C3b deposition on pneumococci was observed. Taken together, pneumococci specifically interact with human C4BP via enolase, which represents an additional mechanism of human complement control by this versatile pathogen.

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Why Do Intravascular Schistosomes Coat Themselves in Glycolytic Enzymes?

2019

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Schistosomes are intravascular parasitic helminths (blood flukes) that infect more than 200 million people globally. Proteomic analysis of the tegument (skin) of these worms has revealed the surprising presence of glycolytic enzymes on the parasite's external surface. Immunolocalization data as well as enzyme activity displayed by live worms confirm that functional glycolytic enzymes are indeed expressed at the host-parasite interface. Since these enzymes are traditionally considered to function intracellularly to drive glycolysis, in an extracellular location they are hypothesized to engage in novel "moonlighting" functions such as immune modulation and blood clot dissolution that promote parasite survival. For instance, several glycolytic enzymes can interact with plasminogen and promote its activation to the thrombolytic plasmin; some can inhibit complement function; some induce B cell proliferation or macrophage apoptosis. Several pathogenic bacteria and protists also express glycolytic enzymes externally, suggesting that moonlighting functions of extracellular glycolytic enzymes can contribute broadly to pathogen virulence. Also see the video abstract here https://youtu.be/njtWZ2y3k_I

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Molecular cloning of an α-enolase from the human filarial parasite Onchocerca volvulus that binds human plasminogen

Cited by 108 publications

References 32 publications

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

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

Enolase ofStreptococcus pneumoniaeBinds Human Complement Inhibitor C4b-Binding Protein and Contributes to Complement Evasion

Why Do Intravascular Schistosomes Coat Themselves in Glycolytic Enzymes?

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