Plasmin(ogen)-binding α-Enolase from Streptococcus pneumoniae: Crystal Structure and Evaluation of Plasmin(ogen)-binding Sites

Ehinger, Stefanie; Schubert, Wolf‐Dieter; Bergmann, Simone; Hammerschmidt, Sven; Heinz, Dirk W.

doi:10.1016/j.jmb.2004.08.088

Cited by 137 publications

(193 citation statements)

References 59 publications

Supporting

Mentioning

180

Contrasting

Order By: Relevance

“…Among the proteins that were down-regulated in the ccpA strain are ones associated with PTSs (SP1177, HPr) (57), glycolysis (SP0605, aldolase; SP1128, enolase), pyrimidine nucleotide biosynthesis (SP0764) (61), and lactate-to-pyruvate interconversion (SP1220) (1). SP1128 has also been shown to bind plasminogen, thereby facilitating host invasion, and contributes to virulence potential (6,20). Some of the proteins that are derepressed in the ccpA strain are associated with sugar uptake (SP1580, SP2108) (50,60) and organic acid metabolism (SP0715, SP1588) (64,68).…”

Section: Resultsmentioning

confidence: 99%

Catabolite Control Protein A (CcpA) Contributes to Virulence and Regulation of Sugar Metabolism in Streptococcus pneumoniae

2005

View full text Add to dashboard Cite

We characterized the role of catabolite control protein A (ccpA) in the physiology and virulence of Streptococcus pneumoniae. S. pneumoniae has a large percentage of its genome devoted to sugar uptake and metabolism, and therefore, regulation of these processes is likely to be crucial for fitness in the nasopharynx and may play a role during invasive disease. In many bacteria, carbon catabolite repression (CCR) is central to such regulation, influencing hierarchical sugar utilization and growth rates. CcpA is the major transcriptional regulator in CCR in several gram-positive bacteria. We show that CcpA functions in CCR of lactose-inducible ␤-galactosidase activity in S. pneumoniae. CCR of maltose-inducible ␣-glucosidase, raffinose-inducible ␣-galactosidase, and cellobiose-inducible ␤-glucosidase is unaffected in the ccpA strain, suggesting that other regulators, possibly redundant with CcpA, control these systems. The ccpA strain is severely attenuated for nasopharyngeal colonization and lung infection in the mouse, establishing its role in fitness on these mucosal surfaces. Comparison of the cell wall fraction of the ccpA and wild-type strains shows that CcpA regulates many proteins in this compartment that are involved in central and intermediary metabolism, a subset of which are required for survival and multiplication in vivo. Both in vitro and in vivo defects were complemented by providing ccpA in trans. Our results demonstrate that CcpA, though not a global regulator of CCR in S. pneumoniae, is required for colonization of the nasopharynx and survival and multiplication in the lung.Carbon metabolism and its regulation are central to prokaryotic life. Sugars serve as the most facile source of carbon and energy, both of which are needed to replenish essential nucleotide cofactors and other metabolites in the cell. When faced with a wide variety of carbon and energy sources, a bacterium has to make metabolic decisions, opting for preferential use of one source over another in order to maintain optimal growth (70, 74).

show abstract

Section: Resultsmentioning

confidence: 99%

Catabolite Control Protein A (CcpA) Contributes to Virulence and Regulation of Sugar Metabolism in Streptococcus pneumoniae

2005

View full text Add to dashboard Cite

show abstract

“…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.…”

Section: Discussionmentioning

confidence: 98%

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

et al. 2008

View full text Add to dashboard Cite

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...

show abstract

“…In the binding of a 30-residue peptide from plasminogen binding Group A streptococcal M-like protein (PAM), VEK-30, to K2 of Pg, Castellino and co-workers (41,42) showed by crystallography and mutagenesis that residues with cationic (Arg and His) and anionic side chains (Glu) arranged spatially on a helix constituted a pseudolysine structure similar to 6-AHA that binds specifically to the LBS of K2. Additional evidence for pseudolysine structures in Pg binding comes from studies of ␣-enolase from Streptococcus pneumoniae, which has a 9-residue internal binding site for Pg containing essential basic (two Lys residues) and acidic (Asp and Glu residues) located on a surface loop (43,44).…”

mentioning

confidence: 99%

Plasminogen Substrate Recognition by the Streptokinase-Plasminogen Catalytic Complex Is Facilitated by Arg253, Lys256, and Lys257 in the Streptokinase β-Domain and Kringle 5 of the Substrate

Tharp

Laha

Panizzi

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

Plasmin(ogen)-binding α-Enolase from Streptococcus pneumoniae: Crystal Structure and Evaluation of Plasmin(ogen)-binding Sites

Cited by 137 publications

References 59 publications

Catabolite Control Protein A (CcpA) Contributes to Virulence and Regulation of Sugar Metabolism in Streptococcus pneumoniae

Catabolite Control Protein A (CcpA) Contributes to Virulence and Regulation of Sugar Metabolism in Streptococcus pneumoniae

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

Plasminogen Substrate Recognition by the Streptokinase-Plasminogen Catalytic Complex Is Facilitated by Arg253, Lys256, and Lys257 in the Streptokinase β-Domain and Kringle 5 of the Substrate

Contact Info

Product

Resources

About