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. ncbi Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus
    Timothy J Foster
    Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland
    Nat Rev Microbiol 12:49-62. 2014
  2. pmc Collagen-binding microbial surface components recognizing adhesive matrix molecule (MSCRAMM) of Gram-positive bacteria inhibit complement activation via the classical pathway
    Mingsong Kang
    Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, Texas 77030, USA
    J Biol Chem 288:20520-31. 2013
  3. pmc Genetic elimination of the binding motif on fibrinogen for the S. aureus virulence factor ClfA improves host survival in septicemia
    Matthew J Flick
    Division of Experimental Hematology and Cancer and Blood Diseases Institute, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Blood 121:1783-94. 2013
  4. ncbi Entry of Bacillus anthracis spores into epithelial cells is mediated by the spore surface protein BclA, integrin α2β1 and complement component C1q
    Qiong Xue
    Center for Inflammatory and Infectious Diseases, Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030, USA
    Cell Microbiol 13:620-34. 2011
  5. pmc Binding of Efb from Staphylococcus aureus to fibrinogen blocks neutrophil adherence
    Ya Ping Ko
    Center for Infectious and Inflammatory Disease, Institute of BioScience and Technology, Texas A and M Health Science Center, Houston, Texas 77030, USA
    J Biol Chem 286:9865-74. 2011
  6. pmc Fibrinogen is a ligand for the Staphylococcus aureus microbial surface components recognizing adhesive matrix molecules (MSCRAMM) bone sialoprotein-binding protein (Bbp)
    Vanessa Vazquez
    Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A and M University System Health Science Center, Houston, Texas 77030, USA
    J Biol Chem 286:29797-805. 2011
  7. 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
  8. 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
  9. 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
  10. 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

Scientific Experts

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

Detail Information

Publications22

  1. ncbi Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus
    Timothy J Foster
    Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland
    Nat Rev Microbiol 12:49-62. 2014
    ..Thus, cell wall-anchored proteins are essential virulence factors for the survival of S. aureus in the commensal state and during invasive infections, and targeting them with vaccines could combat S. aureus infections. ..
  2. pmc Collagen-binding microbial surface components recognizing adhesive matrix molecule (MSCRAMM) of Gram-positive bacteria inhibit complement activation via the classical pathway
    Mingsong Kang
    Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, Texas 77030, USA
    J Biol Chem 288:20520-31. 2013
    ..As a result, C1r2C1s2 was displaced from C1q, and the C1 complex was deactivated. This novel function of the Cna-like MSCRAMMs represents a potential immune evasion strategy that could be used by numerous Gram-positive pathogens. ..
  3. pmc Genetic elimination of the binding motif on fibrinogen for the S. aureus virulence factor ClfA improves host survival in septicemia
    Matthew J Flick
    Division of Experimental Hematology and Cancer and Blood Diseases Institute, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Blood 121:1783-94. 2013
    ..These findings indicate that host fibrin(ogen) and bacterial ClfA are dual determinants of virulence and that therapeutic interventions at the level of fibrinogen could be advantageous in S. aureus septicemia...
  4. ncbi Entry of Bacillus anthracis spores into epithelial cells is mediated by the spore surface protein BclA, integrin α2β1 and complement component C1q
    Qiong Xue
    Center for Inflammatory and Infectious Diseases, Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030, USA
    Cell Microbiol 13:620-34. 2011
    ..These findings suggest a novel mechanism for pathogen entry into host cells as well as a new function for C1q-integrin interactions. The implications of these findings are discussed...
  5. pmc Binding of Efb from Staphylococcus aureus to fibrinogen blocks neutrophil adherence
    Ya Ping Ko
    Center for Infectious and Inflammatory Disease, Institute of BioScience and Technology, Texas A and M Health Science Center, Houston, Texas 77030, USA
    J Biol Chem 286:9865-74. 2011
    ..Taken together, these studies provide insights into how Efb interacts with Fg and suggest that Efb may support bacterial virulence at least in part by impeding Fg-driven leukocyte adhesion events...
  6. pmc Fibrinogen is a ligand for the Staphylococcus aureus microbial surface components recognizing adhesive matrix molecules (MSCRAMM) bone sialoprotein-binding protein (Bbp)
    Vanessa Vazquez
    Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A and M University System Health Science Center, Houston, Texas 77030, USA
    J Biol Chem 286:29797-805. 2011
    ..Also, Bbp interferes with thrombin-induced Fg coagulation. Together these data demonstrate that human Fg is a ligand for Bbp and that Bbp can manipulate the biology of the Fg ligand in the host...
  7. 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...
  8. 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...
  9. 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...
  10. 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...
  11. 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...
  12. 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...
  13. 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...
  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 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...
  16. 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
    ....
  17. 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...
  18. 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...
  19. 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
    ....
  20. 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
    ....
  21. 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...
  22. 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...