BINDING OF BACTERIA TO FIBRONECTIN AN FIBRINOGEN

Summary

Principal Investigator: AXEL HOOK
Affiliation: Texas A and M Health Science Center
Country: USA
Abstract: We request continuing support for our molecular studies of fibronectin (Fn) and fibrinogen (Fib) binding bacterial adhesins. The adhesins present on Gram-positive bacteria such as Staphylococcus aureus and various streptococcal species belong to a family of adhesins that we have called MSCRAMMs, (Microbial Surface Components Recognizing Adhesive Matrix Molecules). The goals for the proposed studies are to determine the structures of the already localized ligand binding sites of the Fn binding MSCRAMMs and the domain(s) recognized in Fn;, We will also initiate an immunological characterization of the MSCRAMMs using a monoclonal antibody approach. The gene encoding the major Fib binding MSCRAMM from S. aureus was recently cloned and sequenced. We will now locate and characterize the active site as well as define the domain recognized in Fib. In these studies, we are using a combination of molecular biological and biochemical techniques. The results of our studies will provide a detailed molecular characterization of the ligand interactions of Fib and Fn binding MSCRAMMs, which represent an early step in the molecular pathogenesis of many infections caused by staphylococcal and streptococcal species. Hence this information will provide the basis for new therapeutic strategies to prevent and treat infections which is much needed particularly at a time when these bacterial species are developing resistance to multiple types of antibiotics.
Funding Period: 1989-12-01 - 2000-03-31
more information: NIH RePORT

Top Publications

  1. pmc A 'Collagen Hug' model for Staphylococcus aureus CNA binding to collagen
    Yinong Zong
    School of Optometry and Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    EMBO J 24:4224-36. 2005
  2. pmc Molecular characterization of the interaction of staphylococcal microbial surface components recognizing adhesive matrix molecules (MSCRAMM) ClfA and Fbl with fibrinogen
    Joan A Geoghegan
    Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland
    J Biol Chem 285:6208-16. 2010
  3. pmc A novel fibronectin binding motif in MSCRAMMs targets F3 modules
    Sabitha Prabhakaran
    Institute of Biosciences and Technology, Texas A and M Health Science Center, College Station, Texas, United States of America
    PLoS ONE 4:e5412. 2009
  4. pmc A family of fibrinogen-binding MSCRAMMs from Enterococcus faecalis
    Jouko Sillanpaa
    Center for Extracellular Matrix Biology, Institute of Biosciences and Technology, Texas A and M University Health Science Center, Houston, TX, USA
    Microbiology 155:2390-400. 2009
  5. pmc The signal peptide of Staphylococcus aureus panton valentine leukocidin LukS component mediates increased adhesion to heparan sulfates
    Anne Tristan
    Universite Lyon 1, Faculte Laennec, Lyon, France
    PLoS ONE 4:e5042. 2009
  6. pmc A structural model of the Staphylococcus aureus ClfA-fibrinogen interaction opens new avenues for the design of anti-staphylococcal therapeutics
    Vannakambadi K Ganesh
    Center for Extracellular Matrix Biology, Institute of Biosciences and Technology, Texas A and M University Health Science Center, Houston, Texas, USA
    PLoS Pathog 4:e1000226. 2008
  7. pmc Identification and phenotypic characterization of a second collagen adhesin, Scm, and genome-based identification and analysis of 13 other predicted MSCRAMMs, including four distinct pilus loci, in Enterococcus faecium
    Jouko Sillanpaa
    Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical School, Houston, TX, USA
    Microbiology 154:3199-211. 2008
  8. pmc Integrins alpha1beta1 and alpha2beta1 are receptors for the rotavirus enterotoxin
    Neung Seon Seo
    Center for Extracellular Matrix Biology, Institute of Biosciences and Technology, Texas A and M University System Health Science Center, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 105:8811-8. 2008
  9. ncbi Evidence for the "dock, lock, and latch" ligand binding mechanism of the staphylococcal microbial surface component recognizing adhesive matrix molecules (MSCRAMM) SdrG
    M Gabriela Bowden
    Center for Extracellular Matrix Biology, Institute of Biosciences and Technology, Texas A and M University System Health Science Center, 2121 W Holcombe Boulevard, Houston, TX 77030, USA
    J Biol Chem 283:638-47. 2008
  10. ncbi The tandem beta-zipper model defines high affinity fibronectin-binding repeats within Staphylococcus aureus FnBPA
    Nicola A G Meenan
    Department of Biology, University of York, P O Box 373, York YO10 5YW, United Kingdom
    J Biol Chem 282:25893-902. 2007

Scientific Experts

  • Anne Tristan
  • MARIA GABRIELA BOWDEN
  • Magnus Hook
  • Vannakambadi K Ganesh
  • Jouko Sillanpaa
  • Barbara E Murray
  • Sreedhar R Nallapareddy
  • Xiaowen Liang
  • Shivasankarappa Gurusiddappa
  • Maria Labandeira-Rey
  • Joan A Geoghegan
  • Timothy J Foster
  • E Magda Barbu
  • Sabitha Prabhakaran
  • Emanuel Smeds
  • Jennifer R Potts
  • Neung Seon Seo
  • Jonathan T Skare
  • Kavindra V Singh
  • Qing Liu
  • Nicola A G Meenan
  • Sthanam V L Narayana
  • Tracey A Dugan
  • Yi Xu
  • J Seshu
  • Yinong Zong
  • R Chris Mackenzie
  • Thomas C Sudhof
  • Agathe Bourgogne
  • Janeu Houston
  • Kate J Kim
  • Budi Utama
  • Joseph M Hyser
  • Ya Ping Ko
  • Vittal P Prakash
  • Sue E Crawford
  • Carl Q Y Zeng
  • Mary K Estes
  • Elisabeth R Wann
  • J Ross Fitzgerald
  • George M Weinstock
  • Xiang Qin
  • Jose J Rivera
  • Jerome Etienne
  • Ulrich Schwarz-Linek
  • Florence Couzon
  • Livia Visai
  • Viviana Valtulina
  • Nicole C Norris
  • Francois Vandenesch
  • Yvonne Benito
  • Vanessa Vazquez
  • Michele Bes
  • Karthe Ponnuraj
  • Eric L Brown
  • Pietro Speziale
  • Elena M Barbu
  • Sivashankarappa Gurusiddappa
  • Sandrine Boisset
  • Jung Hwa Kim
  • M Dolores Esteve-Gassent
  • Danielle A Garsin
  • Stanley L Erlandsen
  • David J McQuillan
  • Jerome P Trzeciakowski
  • Vivian W C Yang
  • Douglas R Keene
  • Agneta Höök

Detail Information

Publications16

  1. pmc A 'Collagen Hug' model for Staphylococcus aureus CNA binding to collagen
    Yinong Zong
    School of Optometry and Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    EMBO J 24:4224-36. 2005
    ..Based on these two structures we propose a dynamic, multistep binding model, called the 'Collagen Hug' that is uniquely designed to allow multidomain collagen binding proteins to bind their extended rope-like ligand...
  2. pmc Molecular characterization of the interaction of staphylococcal microbial surface components recognizing adhesive matrix molecules (MSCRAMM) ClfA and Fbl with fibrinogen
    Joan A Geoghegan
    Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland
    J Biol Chem 285:6208-16. 2010
    ..Fbl variant proteins with alanine substitutions in key residues had reduced affinities for fibrinogen. Thus Fbl and ClfA bind the same site in fibrinogen by similar mechanisms...
  3. pmc A novel fibronectin binding motif in MSCRAMMs targets F3 modules
    Sabitha Prabhakaran
    Institute of Biosciences and Technology, Texas A and M Health Science Center, College Station, Texas, United States of America
    PLoS ONE 4:e5412. 2009
    ..Previous studies from our group showed that BBK32 is a virulence factor in experimental Lyme disease and located the Fn-binding region to residues 21-205 of the lipoprotein...
  4. pmc A family of fibrinogen-binding MSCRAMMs from Enterococcus faecalis
    Jouko Sillanpaa
    Center for Extracellular Matrix Biology, Institute of Biosciences and Technology, Texas A and M University Health Science Center, Houston, TX, USA
    Microbiology 155:2390-400. 2009
    ..Thus, E. faecalis contains a family of MSCRAMMs that structurally and functionally resemble the Fg-binding MSCRAMMs of staphylococci...
  5. pmc The signal peptide of Staphylococcus aureus panton valentine leukocidin LukS component mediates increased adhesion to heparan sulfates
    Anne Tristan
    Universite Lyon 1, Faculte Laennec, Lyon, France
    PLoS ONE 4:e5042. 2009
    ..This mechanism may provide a molecular bridge that enhances the attachment of the S. aureus PVL+ strains to ECM components exposed at damaged epithelial sites...
  6. pmc A structural model of the Staphylococcus aureus ClfA-fibrinogen interaction opens new avenues for the design of anti-staphylococcal therapeutics
    Vannakambadi K Ganesh
    Center for Extracellular Matrix Biology, Institute of Biosciences and Technology, Texas A and M University Health Science Center, Houston, Texas, USA
    PLoS Pathog 4:e1000226. 2008
    ..Our results also suggest that different MSCRAMMs with similar structural organization may have originated from a common ancestor but have evolved to accommodate specific ligand structures...
  7. pmc Identification and phenotypic characterization of a second collagen adhesin, Scm, and genome-based identification and analysis of 13 other predicted MSCRAMMs, including four distinct pilus loci, in Enterococcus faecium
    Jouko Sillanpaa
    Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical School, Houston, TX, USA
    Microbiology 154:3199-211. 2008
    ..faecium isolates tested. The common occurrence of MSCRAMM- and pilus-encoding genes and the presence of a second collagen-binding protein may have important implications for our understanding of this emerging pathogen...
  8. pmc Integrins alpha1beta1 and alpha2beta1 are receptors for the rotavirus enterotoxin
    Neung Seon Seo
    Center for Extracellular Matrix Biology, Institute of Biosciences and Technology, Texas A and M University System Health Science Center, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 105:8811-8. 2008
    ....
  9. ncbi Evidence for the "dock, lock, and latch" ligand binding mechanism of the staphylococcal microbial surface component recognizing adhesive matrix molecules (MSCRAMM) SdrG
    M Gabriela Bowden
    Center for Extracellular Matrix Biology, Institute of Biosciences and Technology, Texas A and M University System Health Science Center, 2121 W Holcombe Boulevard, Houston, TX 77030, USA
    J Biol Chem 283:638-47. 2008
    ....
  10. ncbi The tandem beta-zipper model defines high affinity fibronectin-binding repeats within Staphylococcus aureus FnBPA
    Nicola A G Meenan
    Department of Biology, University of York, P O Box 373, York YO10 5YW, United Kingdom
    J Biol Chem 282:25893-902. 2007
    ..The in vivo relevance of the in vitro binding studies is confirmed by the presence of antibodies in patients with S. aureus infections that specifically recognize complexes of these six high affinity repeats with fibronectin...
  11. ncbi The Enterococcus faecalis MSCRAMM ACE binds its ligand by the Collagen Hug model
    Qing Liu
    Center for Extracellular Matrix Biology, Texas A and M University System Health Science Center, Albert B Alkek Institute of Biosciences and Technology, Houston, Texas 77030, USA
    J Biol Chem 282:19629-37. 2007
    ..Finally, the importance of the residues in the N(2) extension in stabilizing the MSCRAMM-ligand complex is demonstrated by selected point and truncation mutations...
  12. ncbi Staphylococcus aureus Panton-Valentine leukocidin causes necrotizing pneumonia
    Maria Labandeira-Rey
    Center for Extracellular Matrix Biology, Institute of Biosciences and Technology, Texas A and M University System Health Science Center, Houston, TX 77030, USA
    Science 315:1130-3. 2007
    ....
  13. ncbi Decorin modulates fibrin assembly and structure
    Tracey A Dugan
    Center for Extracellular Matrix Biology, Institute of Biosciences and Technology, Texas A and M Health Science Center, 2121 W Holcombe Boulevard, Houston, TX 77030, USA
    J Biol Chem 281:38208-16. 2006
    ..Collectively, these data demonstrate that decorin can regulate fibrin organization and reveal a novel mechanism by which extracellular matrix components can participate in hemostasis, thrombosis, and wound repair...
  14. pmc Endocarditis and biofilm-associated pili of Enterococcus faecalis
    Sreedhar R Nallapareddy
    Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical School at Houston, Houston, Texas 77030, USA
    J Clin Invest 116:2799-807. 2006
    ..These biologically important surface pili, which are antigenic in humans during endocarditis and encoded by a ubiquitous E. faecalis operon, may be a useful immunotarget for studies aimed at prevention and/or treatment of this pathogen...
  15. ncbi Inactivation of the fibronectin-binding adhesin gene bbk32 significantly attenuates the infectivity potential of Borrelia burgdorferi
    J Seshu
    Department of Microbial and Molecular Pathogenesis, Texas A and M University Health Science Center, 407 Reynolds Medical Building, College Station, 77843, USA
    Mol Microbiol 59:1591-601. 2006
    ..burgdorferi-specific pathogenic mechanisms, particularly in the context of dissemination, secondary colonization and/or persistence...
  16. pmc beta-Neurexin is a ligand for the Staphylococcus aureus MSCRAMM SdrC
    E Magda Barbu
    Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, Texas, United States of America
    PLoS Pathog 6:e1000726. 2010
    ..The fact that these two proteins interact when expressed on the appropriate cells demonstrates the functionality of the interaction. Possible implications of this interaction are discussed...