streptolysins

Summary

Summary: Exotoxins produced by certain strains of streptococci, particularly those of group A (STREPTOCOCCUS PYOGENES), that cause HEMOLYSIS.

Top Publications

  1. ncbi Structural basis of pore formation by the bacterial toxin pneumolysin
    Sarah J Tilley
    School of Crystallography and Institute of Structural Molecular Biology, Birkbeck College, Malet Street, London WC1E 7HX, United Kingdom
    Cell 121:247-56. 2005
  2. pmc Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection
    Richard Malley
    Channing Laboratory, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:1966-71. 2003
  3. ncbi The NLRP3 inflammasome is differentially activated by pneumolysin variants and contributes to host defense in pneumococcal pneumonia
    Martin Witzenrath
    Division of Infectious Diseases and Pulmonary Medicine, Department of Internal Medicine, Charite University Medicine Berlin, 13353 Berlin, Germany
    J Immunol 187:434-40. 2011
  4. ncbi Pneumolysin: a double-edged sword during the host-pathogen interaction
    Helen M Marriott
    Section of Infection, Inflammation and Immunity, University of Sheffield School of Medicine and Biomedical Sciences, Sheffield, UK
    Curr Mol Med 8:497-509. 2008
  5. pmc Streptolysin O clearance through sequestration into blebs that bud passively from the plasma membrane
    Peter A Keyel
    Howard Hughes Medical Institute, St Louis, MO 63110, USA
    J Cell Sci 124:2414-23. 2011
  6. pmc Early biofilm formation on microtiter plates is not correlated with the invasive disease potential of Streptococcus pneumoniae
    Anel Lizcano
    Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
    Microb Pathog 48:124-30. 2010
  7. pmc Active Immunization with Pneumolysin versus 23-Valent Polysaccharide Vaccine for Streptococcus pneumoniae Keratitis
    Erin W Norcross
    Department of Microbiology, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA
    Invest Ophthalmol Vis Sci 52:9232-43. 2011
  8. pmc Neutralizing antibodies elicited by a novel detoxified pneumolysin derivative, PlyD1, provide protection against both pneumococcal infection and lung injury
    Danielle Salha
    Sanofi Pasteur, Analytical Research and Development, Toronto, Ontario, Canada
    Infect Immun 80:2212-20. 2012
  9. pmc Construction and immunological characterization of a novel nontoxic protective pneumolysin mutant for use in future pneumococcal vaccines
    Lea Ann S Kirkham
    Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, Scotland, UK
    Infect Immun 74:586-93. 2006
  10. pmc Pneumolysin localizes to the cell wall of Streptococcus pneumoniae
    Katherine E Price
    Howard Hughes Medical Institute and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Bacteriol 191:2163-8. 2009

Detail Information

Publications232 found, 100 shown here

  1. ncbi Structural basis of pore formation by the bacterial toxin pneumolysin
    Sarah J Tilley
    School of Crystallography and Institute of Structural Molecular Biology, Birkbeck College, Malet Street, London WC1E 7HX, United Kingdom
    Cell 121:247-56. 2005
    ..With an oligomer size of up to 44 subunits in the pore, this assembly creates a transmembrane channel 260 A in diameter lined by 176 beta strands...
  2. pmc Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection
    Richard Malley
    Channing Laboratory, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:1966-71. 2003
    ..We conclude that the interaction of pneumolysin with TLR4 is critically involved in the innate immune response to pneumococcus...
  3. ncbi The NLRP3 inflammasome is differentially activated by pneumolysin variants and contributes to host defense in pneumococcal pneumonia
    Martin Witzenrath
    Division of Infectious Diseases and Pulmonary Medicine, Department of Internal Medicine, Charite University Medicine Berlin, 13353 Berlin, Germany
    J Immunol 187:434-40. 2011
    ..The study indicates that a virulence factor polymorphism may substantially affect the recognition of bacteria by the innate immune system...
  4. ncbi Pneumolysin: a double-edged sword during the host-pathogen interaction
    Helen M Marriott
    Section of Infection, Inflammation and Immunity, University of Sheffield School of Medicine and Biomedical Sciences, Sheffield, UK
    Curr Mol Med 8:497-509. 2008
    ....
  5. pmc Streptolysin O clearance through sequestration into blebs that bud passively from the plasma membrane
    Peter A Keyel
    Howard Hughes Medical Institute, St Louis, MO 63110, USA
    J Cell Sci 124:2414-23. 2011
    ..We conclude, therefore, that ectocytosis is an important means for SLO clearance and hypothesize that this is a primary method by which cells defend themselves generally against pore-forming toxins...
  6. pmc Early biofilm formation on microtiter plates is not correlated with the invasive disease potential of Streptococcus pneumoniae
    Anel Lizcano
    Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
    Microb Pathog 48:124-30. 2010
    ..In summary, these studies suggest that the ability to form early biofilms in vitro does not reflect virulence potential. More complex studies are required to determine if biofilm formation is important for virulence...
  7. pmc Active Immunization with Pneumolysin versus 23-Valent Polysaccharide Vaccine for Streptococcus pneumoniae Keratitis
    Erin W Norcross
    Department of Microbiology, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA
    Invest Ophthalmol Vis Sci 52:9232-43. 2011
    ..The purpose of this study was to determine whether active immunization against pneumolysin (PLY), or polysaccharide capsule, protects against the corneal damage associated with Streptococcus pneumoniae keratitis...
  8. pmc Neutralizing antibodies elicited by a novel detoxified pneumolysin derivative, PlyD1, provide protection against both pneumococcal infection and lung injury
    Danielle Salha
    Sanofi Pasteur, Analytical Research and Development, Toronto, Ontario, Canada
    Infect Immun 80:2212-20. 2012
    ..Our detoxified PlyD1 antigen elicits such PLY neutralizing antibodies, thus serving as a candidate vaccine antigen for the prevention of pneumococcal pneumonia...
  9. pmc Construction and immunological characterization of a novel nontoxic protective pneumolysin mutant for use in future pneumococcal vaccines
    Lea Ann S Kirkham
    Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, Scotland, UK
    Infect Immun 74:586-93. 2006
    ..Vaccination with this mutant protects mice from challenge with S. pneumoniae. Incorporation of this mutant pneumolysin into current pneumococcal vaccines may increase their efficacy...
  10. pmc Pneumolysin localizes to the cell wall of Streptococcus pneumoniae
    Katherine E Price
    Howard Hughes Medical Institute and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Bacteriol 191:2163-8. 2009
    ..Hemolytic assays revealed that this cell wall-localized Ply is active. Additionally, cell wall-localized Ply is accessible to extracellular protease and is detergent releasable...
  11. pmc Cholesterol-dependent actin remodeling via RhoA and Rac1 activation by the Streptococcus pneumoniae toxin pneumolysin
    Asparouh I Iliev
    Cell Biophysics Group, European Neuroscience Institute Göttingen, Waldweg 33, 37073 Gottingen, Germany
    Proc Natl Acad Sci U S A 104:2897-902. 2007
    ..Thus, that our experiments show small GTPase activation by a cholesterol-dependent cytolysin suggests a membrane cholesterol-dependent activation mechanism...
  12. pmc Pneumococcal pneumolysin and H(2)O(2) mediate brain cell apoptosis during meningitis
    Johann S Braun
    Department of Infectious Diseases, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Clin Invest 109:19-27. 2002
    ..Two bacterial toxins, pneumolysin and, to a lesser extent, H(2)O(2), induce apoptosis by translocation of AIF, suggesting new neuroprotective strategies for pneumococcal meningitis...
  13. pmc Epithelial cells are sensitive detectors of bacterial pore-forming toxins
    Adam J Ratner
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 281:12994-8. 2006
    ..Osmosensing may thus represent a novel innate immune response to a common bacterial virulence strategy...
  14. pmc The role of pneumolysin in pneumococcal pneumonia and meningitis
    R A Hirst
    Department of Infection, Inflamation and Immunity, University of Leicester, Leicester, UK
    Clin Exp Immunol 138:195-201. 2004
    ..One of the main toxins released from pneumococci is the membrane pore forming toxin pneumolysin. Here we review the extensive studies on the role of pneumolysin in the pathogenesis of pneumococcal diseases...
  15. ncbi Pneumolysin-induced CXCL8 production by nasopharyngeal epithelial cells is dependent on calcium flux and MAPK activation via Toll-like receptor 4
    Semih Dogan
    School of Clinical Sciences, University of Bristol, Bristol, UK
    Microbes Infect 13:65-75. 2011
    ..This may be important in regulating nasopharyngeal immunity against pneumococcal colonization...
  16. ncbi The conserved undecapeptide shared by thiol-activated cytolysins is involved in membrane binding
    T Jacobs
    Molecular Immunology, GBF National Center for Biotechnology, Mascheroder Weg 1, D 38124, Braunschweig, Germany
    FEBS Lett 459:463-6. 1999
    ..These results confirm the model of cytolysin binding suggested by structural data...
  17. pmc Upper and lower respiratory tract infection by Streptococcus pneumoniae is affected by pneumolysin deficiency and differences in capsule type
    Aras Kadioglu
    Department of Microbiology and Immunology, University of Leicester, Leicester, LE1 United Kingdom
    Infect Immun 70:2886-90. 2002
    ..The combination of capsule type and genetic background also determined virulence. Thus, the wild-type serotype 3 strain was virulent, whereas the capsule-switched mutant was avirulent...
  18. ncbi NAD+-glycohydrolase acts as an intracellular toxin to enhance the extracellular survival of group A streptococci
    Angela L Bricker
    Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USA
    Mol Microbiol 44:257-69. 2002
    ..We conclude that NAD+-glycohydrolase is a novel type of bacterial toxin that acts intracellularly in the infected host to enhance the survival and proliferation of an extracellular pathogen...
  19. ncbi Role of pneumolysin for the development of acute lung injury in pneumococcal pneumonia
    Martin Witzenrath
    Charite Universitatsmedizin Berlin, Department of Internal Medicine Infectious Diseases and Pulmonary Medicine, Berlin, Germany
    Crit Care Med 34:1947-54. 2006
    ..In a mouse model, we observed early-onset lung microvascular leakage after pulmonary infection with Streptococcus pneumoniae, and we hypothesized that the important virulence factor pneumolysin may be the direct causative agent...
  20. ncbi Hyaluronidase augments pneumolysin-mediated injury to human ciliated epithelium
    C Feldman
    Division of Pulmonology, Department of Medicine, Johannesburg Hospital and University of the Witwatersrand, 7 York Road, Parktown, 2193 Johannesburg, South Africa
    Int J Infect Dis 11:11-5. 2007
    ..The main objective of this study was to investigate the effects of pneumococcal hyaluronidase (0.1-10microg/ml), alone and in combination with pneumolysin (50 and 100ng/ml), on human ciliated epithelium...
  21. pmc Streptolysin O inhibits clathrin-dependent internalization of group A Streptococcus
    Lauren K Logsdon
    Division of Infectious Diseases, Children s Hospital Boston and Harvard Medical School, Boston, Massachusetts, USA
    MBio 2:e00332-10. 2011
    ..We conclude that SLO interferes with the internalization of GAS through local perturbation of the keratinocyte cell membrane and disruption of a clathrin-dependent uptake pathway...
  22. pmc Identification of a novel pneumococcal vaccine antigen preferentially expressed during meningitis in mice
    Layla K Mahdi
    Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia
    J Clin Invest 122:2208-20. 2012
    ..Our results provide the basis of a strategy that can be adapted to identify genes that contribute to the development of meningitis caused by other pathogens...
  23. pmc Protein kinase C-α and arginase I mediate pneumolysin-induced pulmonary endothelial hyperpermeability
    Rudolf Lucas
    Vascular Biology Center and Dept of Pharmacology and Toxicology, Georgia Health Sciences University, 1459 Laney Walker Blvd, Augusta, GA 30912 2500, USA
    Am J Respir Cell Mol Biol 47:445-53. 2012
    ..These results identify PKC-α and arginase I as potential upstream and downstream therapeutic targets in PLY-induced pulmonary endothelial dysfunction...
  24. ncbi Extracellular group A Streptococcus induces keratinocyte apoptosis by dysregulating calcium signalling
    Colette Cywes Bentley
    Channing Laboratory, Brigham and Women s Hospital, Boston, MA 02115, USA
    Cell Microbiol 7:945-55. 2005
    ..We propose that cell signalling initiated by extracellular GAS compromises the epithelial barrier by inducing premature keratinocyte differentiation and apoptosis, thereby facilitating GAS invasion of deeper tissues...
  25. pmc Export requirements of pneumolysin in Streptococcus pneumoniae
    Katherine E Price
    Tufts University School of Medicine and Howard Hughes Medical Institute, Department of Molecular Biology and Microbiology, Boston, Massachusetts, USA
    J Bacteriol 194:3651-60. 2012
    ..We show that B. subtilis can export Ply, suggesting that the export pathway is conserved. Finally, through truncation and domain swapping analyses, we show that export is dependent on domain 2 of Ply...
  26. pmc Immunization with a combination of three pneumococcal proteins confers additive and broad protection against Streptococcus pneumoniae Infections in Mice
    Kaifeng Wu
    Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine Ministry of Education, Chongqing Medical University, Chongqing 400016, People s Republic of China
    Infect Immun 78:1276-83. 2010
    ..These results indicate that system immunization with the combination of pneumococcal antigens could provide an additive and broad protection against Streptococcus pneumoniae in pneumonia and sepsis infection models...
  27. pmc Pneumolysin with low hemolytic activity confers an early growth advantage to Streptococcus pneumoniae in the blood
    Richard M Harvey
    Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide 5005, Australia
    Infect Immun 79:4122-30. 2011
    ..In summary, we show that low-hemolytic-activity Ply alleles contribute to systemic virulence and may provide a survival advantage in the blood. Moreover, pneumococci expressing such alleles remain vulnerable to Ply-based vaccines...
  28. ncbi Tumor suppressor CYLD regulates acute lung injury in lethal Streptococcus pneumoniae infections
    Jae Hyang Lim
    Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA
    Immunity 27:349-60. 2007
    ..Thus, CYLD is detrimental for host survival, thereby indicating a mechanism underlying the high early mortality of pneumococcal pneumonia...
  29. ncbi A protein-based pneumococcal vaccine protects rhesus macaques from pneumonia after experimental infection with Streptococcus pneumoniae
    Philippe DeNoel
    GlaxoSmithKline Biologicals, Rixensart, Belgium
    Vaccine 29:5495-501. 2011
    ..In conclusion, AS02-adjuvanted PhtD-dPly vaccine protects against S. pneumoniae-induced pneumonia. It is probable that the protection is at least partially mediated by PhtD- and Ply-specific antibodies...
  30. pmc Streptococcus pneumoniae-induced inhibition of rat ependymal cilia is attenuated by antipneumolysin antibody
    Robert A Hirst
    Department of Infection, Immunity and Inflammation, University of Leicester, LE2 7LX, UK
    Infect Immun 72:6694-8. 2004
    ..These data show that antibiotic lysis of Streptococcus pneumoniae can be detrimental to the ciliated ependyma and that antipneumolysin antibody may have a therapeutic potential...
  31. pmc Identification of invasive serotype 1 pneumococcal isolates that express nonhemolytic pneumolysin
    Lea Ann S Kirkham
    Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland
    J Clin Microbiol 44:151-9. 2006
    ..Pneumolysin is generally conserved throughout all serotypes of S. pneumoniae and is essential for full invasive disease; however, it appears that serotype 1 ST306 does not require hemolytically active pneumolysin to cause IPD...
  32. pmc Cytotoxic effects of streptolysin o and streptolysin s enhance the virulence of poorly encapsulated group a streptococci
    Gabriele Sierig
    Channing Laboratory and Division of Infectious Diseases, Brigham and Women s Hospital, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
    Infect Immun 71:446-55. 2003
    ..Compared to SLO, SLS in this strain background has a more modest influence on GAS pathogenicity and the effect does not appear to involve bacterial resistance to phagocytosis...
  33. pmc Delivery of proteins into living cells by reversible membrane permeabilization with streptolysin-O
    I Walev
    Institute of Medical Microbiology and Hygiene, Johannes Gutenberg University, 55101 Mainz, Germany
    Proc Natl Acad Sci U S A 98:3185-90. 2001
    ..botulinum C2-toxin resulted in enhanced secretion in cells. The presented method for introducing proteins into living cells should find multifaceted application in cell biology...
  34. ncbi Novel mucosal vaccines generated by genetic conjugation of heterologous proteins to pneumolysin (PLY) from Streptococcus pneumoniae
    Gill Douce
    Division of Infection and Immunity, Faculty of Biomedical and Life Sciences, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow G12 8TA, UK
    Vaccine 28:3231-7. 2010
    ....
  35. ncbi Proinflammatory interactions of pneumolysin with human neutrophils
    R Cockeran
    Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Institute for Pathology, University of Pretoria, Pretoria 0001, South Africa
    J Infect Dis 183:604-11. 2001
    ..Pneumolysin potentiates the proinflammatory activities of neutrophils by a pore-forming mechanism resulting in Ca2+ influx...
  36. ncbi Immunizations with pneumococcal surface protein A and pneumolysin are protective against pneumonia in a murine model of pulmonary infection with Streptococcus pneumoniae
    David E Briles
    Department of Microbiology, University of Alabama at Birmingham, USA
    J Infect Dis 188:339-48. 2003
    ....
  37. pmc Contributions of pneumolysin, pneumococcal surface protein A (PspA), and PspC to pathogenicity of Streptococcus pneumoniae D39 in a mouse model
    Abiodun D Ogunniyi
    School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia
    Infect Immun 75:1843-51. 2007
    ..These findings further demonstrate that the mechanism of pneumococcal pathogenesis is highly complex and multifactorial but ascribes a role for each of these virulence proteins, alone or in combination, in the process...
  38. pmc THP-1 monocytes up-regulate intercellular adhesion molecule 1 in response to pneumolysin from Streptococcus pneumoniae
    Justin Thornton
    Department of Microbiology, University of Mississippi Medical Center, Jackson, 39216, USA
    Infect Immun 73:6493-8. 2005
    ..These data indicate that PLY induces transcription and production of a cell adhesion molecule involved in the inflammatory response that may play a role in pneumococcal infection...
  39. pmc The autolytic enzyme LytA of Streptococcus pneumoniae is not responsible for releasing pneumolysin
    P Balachandran
    Department of Microbiology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
    J Bacteriol 183:3108-16. 2001
    ..Finally, under some infection conditions, mutations in pneumolysin and autolysin had different effects on virulence...
  40. pmc Tumor suppressor cylindromatosis acts as a negative regulator for Streptococcus pneumoniae-induced NFAT signaling
    Tomoaki Koga
    Department of Microbiology and Immunology and Cardiovascular Research Institute, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 283:12546-54. 2008
    ..pneumoniae infections through the NFAT-dependent mechanism and further identify CYLD as a negative regulator for NFAT signaling, thereby opening up new therapeutic targets for these diseases...
  41. pmc Streptococcus pyogenes cytolysin-mediated translocation does not require pore formation by streptolysin O
    N Goundo Magassa
    Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri 63110 1093, USA
    EMBO Rep 11:400-5. 2010
    ..Moreover, despite the ability of mutants to translocate SPN, their cytotoxic effect requires SLO pore formation...
  42. ncbi Streptococcus pneumoniae deficient in pneumolysin or autolysin has reduced virulence in meningitis
    Robert A Hirst
    Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester, United Kingdom
    J Infect Dis 197:744-51. 2008
    ..The role played by pneumolysin and autolysin in pneumococcal meningitis is poorly understood...
  43. pmc Decreased virulence of a pneumolysin-deficient strain of Streptococcus pneumoniae in murine meningitis
    Andreas Wellmer
    Department of Neurology, University of Gottingen, Gottingen, Germany
    Infect Immun 70:6504-8. 2002
    ..Cerebellar and spleen bacterial titers, meningeal inflammation, and neuronal damage scores remained uninfluenced by the lack of any of the virulence factors...
  44. pmc Cholesterol as treatment for pneumococcal keratitis: cholesterol-specific inhibition of pneumolysin in the cornea
    Mary E Marquart
    Department of Microbiology, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA
    Invest Ophthalmol Vis Sci 48:2661-6. 2007
    ..The purpose of this study was to determine whether cholesterol, the host cell receptor for pneumolysin of Streptococcus pneumoniae, could effectively treat pneumococcal keratitis...
  45. ncbi Comparison of the effects of macrolides, amoxicillin, ceftriaxone, doxycycline, tobramycin and fluoroquinolones, on the production of pneumolysin by Streptococcus pneumoniae in vitro
    R Anderson
    Medical Research Council MRC Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria, and Tshwane Academic Division of the National Health Laboratory Service, South Africa
    J Antimicrob Chemother 60:1155-8. 2007
    ....
  46. pmc Pneumolysin, PspA, and PspC contribute to pneumococcal evasion of early innate immune responses during bacteremia in mice
    Lisa R Quin
    Department of Microbiology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA
    Infect Immun 75:2067-70. 2007
    ..Finally, blood clearance assays demonstrated that there was enhanced clearance of Deltaply PspA(-) PspC(-) pneumococci compared to the clearance of nonencapsulated pneumococci...
  47. pmc Direct transmembrane interaction between actin and the pore-competent, cholesterol-dependent cytolysin pneumolysin
    Sabrina Hupp
    DFG Membrane Cytoskeleton Interaction Group, Institute of Pharmacology and Toxicology and Rudolf Virchow Centre for Experimental Biomedical Science, University of Wurzburg, Versbacherstr 9, 97078 Wurzburg, Germany
    J Mol Biol 425:636-46. 2013
    ..Our results demonstrate the first example of a direct interaction of a pore-forming toxin with cytoskeletal components, suggesting that the cross talk between pore-forming cytolysins and cells is more complex than previously thought...
  48. pmc Combined contributions of streptolysin O and streptolysin S to virulence of serotype M5 Streptococcus pyogenes strain Manfredo
    Michael C Fontaine
    School of Cell and Molecular Biosciences, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom
    Infect Immun 71:3857-65. 2003
    ....
  49. ncbi Virulence factors and the pathogenesis of disease caused by Streptococcus pneumoniae
    T J Mitchell
    Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland, UK
    Res Microbiol 151:413-9. 2000
    ..The use of molecular approaches to identifying and studying putative virulence factors in combination with the application of animal models has allowed some of the mechanisms of the disease process to be defined...
  50. pmc Persistence of pneumolysin in the cerebrospinal fluid of patients with pneumococcal meningitis is associated with mortality
    Emma C Wall
    Clinical Research Group, Liverpool School of Tropical Medicine, United Kingdom
    Clin Infect Dis 54:701-5. 2012
    ..In patient samples we showed that pneumolysin levels in CSF remained high after 48 hours in nonsurvivors of meningitis compared with survivors. Selective antipneumolysin treatment may present a novel therapeutic option...
  51. ncbi Astrocytic tissue remodeling by the meningitis neurotoxin pneumolysin facilitates pathogen tissue penetration and produces interstitial brain edema
    Sabrina Hupp
    DFG Membrane Cytoskeleton Interaction Group, Institute of Pharmacology and Toxicology and Rudolf Virchow Center for Experimental Medicine, University of Wurzburg, Versbacherstr 9, 97078 Wurzburg, Germany
    Glia 60:137-46. 2012
    ..We suggest that PLY can increase the permeability of brain tissue toward pathogenic factors and bacteria in the course of meningitis, thus contributing to the deterioration caused by the disease...
  52. pmc Changes in astrocyte shape induced by sublytic concentrations of the cholesterol-dependent cytolysin pneumolysin still require pore-forming capacity
    Christina Förtsch
    DFG Membrane, Cytoskeleton Interaction Group, Institute of Pharmacology and Toxicology and Rudolf Virchow Center for Experimental Medicine, University of Wurzburg, Versbacherstr 9, 97078 Wurzburg, Germany
    Toxins (Basel) 3:43-62. 2011
    ....
  53. ncbi Nitric oxide levels regulate macrophage commitment to apoptosis or necrosis during pneumococcal infection
    Helen M Marriott
    Division of Genomic Medicine, University of Sheffield School of Medicine and Biomedical Sciences, Sheffield, UK
    FASEB J 18:1126-8. 2004
    ..These results illustrate important roles for NO in the integration of host defense and regulation of inflammation in human macrophages...
  54. pmc Specific behavior of intracellular Streptococcus pyogenes that has undergone autophagic degradation is associated with bacterial streptolysin O and host small G proteins Rab5 and Rab7
    Atsuo Sakurai
    Department of Pediatric Dentistry, Tokyo Dental College, 1 2 2 Masago, Mihama ku, Chiba 261 8502, Japan
    J Biol Chem 285:22666-75. 2010
    ..This intracellular behavior of GAS is unique and distinct from that of other types of bacterial invaders. Our results provide a new picture of GAS infection and host-cell responses in epithelial cells...
  55. ncbi The molecular mechanism of pneumolysin, a virulence factor from Streptococcus pneumoniae
    J Rossjohn
    The Ian Potter Foundation Protein Crystallography Laboratory, St Vincent s Institute of Medical Research, 41 Victoria Parade, Fitzroy, Victoria, 3065, Australia
    J Mol Biol 284:449-61. 1998
    ....
  56. ncbi Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2
    A Yoshimura
    Maxwell Finland Laboratory for Infectious Diseases, Boston University School of Medicine, Boston Medical Center, MA 02118, USA
    J Immunol 163:1-5. 1999
    ..Soluble peptidoglycan substituted for whole organisms. These data suggest that the similarity of clinical response to invasive infection by Gram-positive and Gram-negative bacteria is due to bacterial recognition via similar TLRs...
  57. ncbi Neurotoxicity of pneumolysin, a major pneumococcal virulence factor, involves calcium influx and depends on activation of p38 mitogen-activated protein kinase
    Argyrios K Stringaris
    Department of Neurology, University of Gottingen, 37075, Gottingen, Germany
    Neurobiol Dis 11:355-68. 2002
    ..Modulation of cell death pathways activated by pneumolysin may influence the outcome of pneumococcal meningitis...
  58. pmc Cytolysin-dependent evasion of lysosomal killing
    Anders Hakansson
    Channing Laboratory, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:5192-7. 2005
    ....
  59. ncbi Dose-dependent activation of microglial cells by Toll-like receptor agonists alone and in combination
    Sandra Ebert
    Department of Neurology, University of Gottingen, Robert Koch Str 40, 37075 Gottingen, Germany
    J Neuroimmunol 159:87-96. 2005
    ..Costimulation with submaximum concentrations was additive or supraadditive, suggesting that even low concentrations of products of infectious agents can lead to microglial activation via TLRs...
  60. pmc Pneumolysin potentiates production of prostaglandin E(2) and leukotriene B(4) by human neutrophils
    R Cockeran
    Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Institute for Pathology, University of Pretoria, Pretoria, South Africa
    Infect Immun 69:3494-6. 2001
    ..These interactions of pneumolysin with neutrophils may result in dysregulation of inflammatory responses during pneumococcal infection...
  61. ncbi The effects of pneumolysin and hydrogen peroxide, alone and in combination, on human ciliated epithelium in vitro
    C Feldman
    Division of Pulmonology, Department of Medicine, Johannesburg Hospital, University of the Witwatersrand, South Africa
    Respir Med 96:580-5. 2002
    ..These actions of pneumolysin and H2O2 may contribute to the pathogenesis of respiratory tract infections caused by the pneumococcus...
  62. pmc Incompetence of neutrophils to invasive group A streptococcus is attributed to induction of plural virulence factors by dysfunction of a regulator
    Manabu Ato
    Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan
    PLoS ONE 3:e3455. 2008
    ..These results suggest that the abilities of GAS to abrogate PMN functions can determine the onset and severity of invasive GAS infection...
  63. pmc Functional analysis of pneumolysin by use of monoclonal antibodies
    J R de los Toyos
    Facultad de Medicina, Universidad de Oviedo, Spain
    Infect Immun 64:480-4. 1996
    ..This site is engaged in the oligomerization process involved in the formation of pores in cell membranes. Two of these epitopes are also present in the related toxin perfringolysin O...
  64. ncbi Differential role of p38 mitogen activated protein kinase for cellular recovery from attack by pore-forming S. aureus alpha-toxin or streptolysin O
    Matthias Husmann
    Institute of Medical Microbiology and Hygiene, Johannes Gutenberg University, Mainz, Hochhaus am Augustusplatz, 55131 Mainz, Germany
    Biochem Biophys Res Commun 344:1128-34. 2006
    ..In contrast, blockade of p38 in SLO permeabilized cells did not affect the capacity of the cells to replenish their ATP stores...
  65. ncbi Human lung mast cells mediate pneumococcal cell death in response to activation by pneumolysin
    Glenn Cruse
    Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester Medical School, Leicester, United Kingdom
    J Immunol 184:7108-15. 2010
    ..This suggests that mast cells provide an early warning system and potentially limit pneumococcal dissemination early in the course of invasive pulmonary pneumococcal disease...
  66. ncbi Pneumococcal carriage and otitis media induce salivary antibodies to pneumococcal surface adhesin a, pneumolysin, and pneumococcal surface protein a in children
    B Simell
    Department of Vaccines, National Public Health Institute, Helsinki, Finland
    J Infect Dis 183:887-96. 2001
    ..The findings indicate that pneumococcal carriage and AOM induce local production of anti-PsaA, anti-Ply, and anti-PspA antibodies early in life...
  67. pmc Pneumolysin, a protein toxin of Streptococcus pneumoniae, induces nitric oxide production from macrophages
    J S Braun
    Department of Infectious Diseases, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Infect Immun 67:3750-6. 1999
    ..The properties of Pln, previously identified as a pore-forming hemolysin, also include a role as a general inflammatory agonist...
  68. pmc Simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in suspected cases of meningitis and septicemia using real-time PCR
    C E Corless
    Meningococcal Reference Unit, Manchester Public Health Laboratory, Withington Hospital, Manchester M20 2LR, United Kingdom
    J Clin Microbiol 39:1553-8. 2001
    ..The ctrA primer set used in the multiplex PCR was found to be more sensitive (P < 0.0001) than the ctrA primers that had been used for meningococcal PCR testing at that time...
  69. pmc Pneumolysin is the main inducer of cytotoxicity to brain microvascular endothelial cells caused by Streptococcus pneumoniae
    G Zysk
    Department of Medical Microbiology and Virology, University of Duesseldorf, Duesseldorf, Germany
    Infect Immun 69:845-52. 2001
    ..The results show that pneumolysin is an important component for damaging the BBB and may contribute to the entry of pneumococci into the cerebral compartment and to the development of brain edema in pneumococcal meningitis...
  70. pmc Reduced release of pneumolysin by Streptococcus pneumoniae in vitro and in vivo after treatment with nonbacteriolytic antibiotics in comparison to ceftriaxone
    Annette Spreer
    Department of Neurology, University of Gottingen, Gottingen, Germany
    Antimicrob Agents Chemother 47:2649-54. 2003
    ....
  71. ncbi Intracellular Ca(2+) operates a switch between repair and lysis of streptolysin O-perforated cells
    E B Babiychuk
    Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, Switzerland
    Cell Death Differ 16:1126-34. 2009
    ..These findings show that the extent of [Ca(2+)](i) elevation determines the fate of targeted cells and establishes how different Ca(2+)-dependent mechanisms facilitate either cell survival or death...
  72. pmc The streptococcal exotoxin streptolysin O activates mast cells to produce tumor necrosis factor alpha by p38 mitogen-activated protein kinase- and protein kinase C-dependent pathways
    Michael Stassen
    Institute of Immunology Institute of Medical Microbiology, Johannes Gutenberg University, Mainz, Germany
    Infect Immun 71:6171-7. 2003
    ..However, hyperstimulation of mast cells might also lead to overproduction of TNF-alpha, which would then promote the development of toxic streptococcal syndromes...
  73. ncbi Enhancement of streptolysin O activity and intrinsic cytotoxic effects of the group A streptococcal toxin, NAD-glycohydrolase
    Athanasios Michos
    Division of Infectious Diseases, Children s Hospital Boston, Massachusetts 02215, USA
    J Biol Chem 281:8216-23. 2006
    ..Together, the results have provided mechanistic insight into the cytotoxic effects of a unique bipartite bacterial toxin...
  74. pmc Pneumococcal behavior and host responses during bronchopneumonia are affected differently by the cytolytic and complement-activating activities of pneumolysin
    Rania Jounblat
    Department of Microbiology and Immunology, University of Leicester, University Road, Leicester, LE1 9HN, UK
    Infect Immun 71:1813-9. 2003
    ..The complement-activating activity of pneumolysin affected the accumulation of T cells, whereas the toxin's cytolytic activity influenced neutrophil recruitment into lung tissue...
  75. pmc Nucleotide sequence of the gene for perfringolysin O (theta-toxin) from Clostridium perfringens: significant homology with the genes for streptolysin O and pneumolysin
    R K Tweten
    Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City 73190
    Infect Immun 56:3235-40. 1988
    ..The location of these 12 residues was conserved in all three toxins when the primary sequences were aligned for maximum homology...
  76. pmc Immunization with pneumolysin protects against both retinal and global damage caused by Streptococcus pneumoniae endophthalmitis
    Melissa E Sanders
    Department of Microbiology, University of Mississippi Medical Center, Jackson, MS 39216, USA
    J Ocul Pharmacol Ther 26:571-7. 2010
    ..To determine whether immunization with pneumolysin (PLY) protects against pneumococcal endophthalmitis...
  77. pmc Induction of necrosis and apoptosis of neutrophil granulocytes by Streptococcus pneumoniae
    G Zysk
    Institute of Medical Microbiology and Virology, University of Dusseldorf, Dusseldorf, Germany
    Clin Exp Immunol 122:61-6. 2000
    ..These results demonstrated that pneumococci induce PMN cell death. Depending on the intensity of the stimulus, PMN necrosis and apoptosis were observed...
  78. ncbi Ultrastructural analysis of the membrane insertion of domain 3 of streptolysin O
    Kachiko Sekiya
    Laboratory of Electron Microscopy, School of Pharmacy, Kitasato University, 5 9 1 Shirokane, Minato ku, Tokyo 108 8641, Japan
    Microbes Infect 9:1341-50. 2007
    ..On the basis of a model of the oligomeric structure of SLO, we propose some new details of the mechanism of hemolysis by SLO...
  79. pmc Discovery of a widely distributed toxin biosynthetic gene cluster
    Shaun W Lee
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 105:5879-84. 2008
    ..Given our findings, it is likely that the discovery of similar peptidic toxins will rapidly expand to existing and emerging genomes...
  80. ncbi DNA vaccines based on genetically detoxified derivatives of pneumolysin fail to protect mice against challenge with Streptococcus pneumoniae
    Daniela M Ferreira
    Centro de Biotecnologia, Instituto Butantan, Sao Paulo, SP, Brazil
    FEMS Immunol Med Microbiol 46:291-7. 2006
    ..Immunization with DNA vaccines expressing pneumolysoids, on the other hand, induced a significantly lower antibody response and no protection was observed...
  81. ncbi Clinical use and interpretation of group A streptococcal antibody tests: a practical approach for the pediatrician or primary care physician
    Anita Shet
    Department of Pediatrics, World Health Organization Collaborating Center for Reference and Research on Streptococci, University of Minnesota Medical School, Minneapolis, USA
    Pediatr Infect Dis J 21:420-6; quiz 427-30. 2002
  82. pmc Pneumolysin-mediated activation of NFkappaB in human neutrophils is antagonized by docosahexaenoic acid
    H Fickl
    Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, University of Pretoria, Pretoria
    Clin Exp Immunol 140:274-81. 2005
    ....
  83. pmc Pneumococcal virulence factors: structure and function
    M J Jedrzejas
    Department of Microbiology, University of Alabama at Birmingham, 933 19th Street South, Birmingham, AL 35294
    Microbiol Mol Biol Rev 65:187-207 ; first page, table of contents. 2001
    ....
  84. ncbi Rapid microtubule bundling and stabilization by the Streptococcus pneumoniae neurotoxin pneumolysin in a cholesterol-dependent, non-lytic and Src-kinase dependent manner inhibits intracellular trafficking
    Asparouh I Iliev
    Laboratory for Molecular and Cellular Systems, Department of Neuro and Sensory Physiology, Instutute for Physiology and Pathophysiology, University Medicine Gottingen, 37073 Gottingen, Germany
    Mol Microbiol 71:461-77. 2009
    ....
  85. ncbi Assembly and topography of the prepore complex in cholesterol-dependent cytolysins
    Alejandro P Heuck
    Department of Medical Biochemistry and Genetics, Texas A and M University System Health Science Center, College Station, Texas 77843 1114, USA
    J Biol Chem 278:31218-25. 2003
    ....
  86. pmc Repair of injured plasma membrane by rapid Ca2+-dependent endocytosis
    Vincent Idone
    Section of Microbial Pathogenesis and 2Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA
    J Cell Biol 180:905-14. 2008
    ..These findings provide an important new insight into how cells protect themselves not only from mechanical injury but also from microbial toxins and pore-forming proteins produced by the immune system...
  87. ncbi Tissue-specific contributions of pneumococcal virulence factors to pathogenesis
    Carlos J Orihuela
    Department of Infectious Diseases, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    J Infect Dis 190:1661-9. 2004
    ..We conclude that transitions between body sites require virulence determinants distinct from those involved in organ-specific replication...
  88. pmc Prospective study to determine clinical relevance of detection of pneumococcal DNA in sera of children by PCR
    R Dagan
    Pediatric Infectious Disease Unit, Soroka University Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel
    J Clin Microbiol 36:669-73. 1998
    ....
  89. pmc The apoptotic response to pneumolysin is Toll-like receptor 4 dependent and protects against pneumococcal disease
    Amit Srivastava
    Division of Infectious Diseases, Department of Medicine, Children s Hospital, Boston, MA 02115, USA
    Infect Immun 73:6479-87. 2005
    ..Overall, our results strongly suggest that protection against pneumococcal disease is dependent on the TLR4-mediated enhancement of pneumolysin-induced apoptosis...
  90. ncbi Streptococcus pneumoniae: the role of apoptosis in host defense and pathogenesis
    Helen M Marriott
    Division of Genomic Medicine, F Floor, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK
    Int J Biochem Cell Biol 38:1848-54. 2006
    ..Apoptosis induction may be harmful or potentially beneficial during pneumococcal infection and understanding its function in each setting is essential to allow specific therapeutic intervention...
  91. pmc Protection against Streptococcus pneumoniae elicited by immunization with pneumolysin and CbpA
    A D Ogunniyi
    Department of Molecular Biosciences, Adelaide University, Adelaide, South Australia 5005, Australia
    Infect Immun 69:5997-6003. 2001
    ..Mice immunized with PdB in MPL plus AlPO4 were also significantly better protected than mice that received PdB in AlPO4 alone...
  92. pmc Structural and functional dissection of the heterocyclic peptide cytotoxin streptolysin S
    Douglas A Mitchell
    Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA
    J Biol Chem 284:13004-12. 2009
    ..This new structural information has ramifications for future antimicrobial therapies...
  93. ncbi Pneumococci induced TLR- and Rac1-dependent NF-kappaB-recruitment to the IL-8 promoter in lung epithelial cells
    Bernd Schmeck
    Department of Internal Medicine Infectious Diseases, Charite Universitatsmedizin Berlin, Berlin, Germany
    Am J Physiol Lung Cell Mol Physiol 290:L730-L737. 2006
    ..In summary, these results suggest that S. pneumoniae activate human epithelial cells by TLR1/2 and a phosphatidylinositol 3-kinase- and Rac1-dependent NF-kappaB-recruitment to the IL-8 promoter...
  94. pmc Pneumolysin-induced complement depletion during experimental pneumococcal bacteremia
    R B Alcantara
    Veterans Affairs Medical Center, Omaha, Nebraska 68105, USA
    Infect Immun 69:3569-75. 2001
    ..These studies suggest that under limiting concentrations of complement, the expression of pneumolysin by pneumococci has a significant, negative effect on serum complement levels and reduces serum opsonic activity...
  95. ncbi A specific and ultrasensitive chemiluminescent sandwich ELISA test for the detection and quantitation of pneumolysin
    M D Cima-Cabal
    , Facultad de Medicina, Universidad de Oviedo, Spain
    J Immunoassay Immunochem 22:99-112. 2001
    ..The test is highly specific as no other purified toxins or human pneumonia- or meningitis-associated bacteria yielded false-positive results. This specific and highly sensitive method could help in the diagnosis of human infections...
  96. ncbi Resealing of large transmembrane pores produced by streptolysin O in nucleated cells is accompanied by NF-kappaB activation and downstream events
    Iwan Walev
    Institute of Medical Microbiology, Johannes Gutenberg University Mainz, D 55101 Mainz, Germany
    FASEB J 16:237-9. 2002
    ..The study provides definitive evidence that a transient transmembrane pore suffices to trigger productive transcriptional activation in a target cell...
  97. pmc MKP1 regulates the induction of MUC5AC mucin by Streptococcus pneumoniae pneumolysin by inhibiting the PAK4-JNK signaling pathway
    Un Hwan Ha
    Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 283:30624-31. 2008
    ..These studies provide novel insights into the molecular mechanisms underlying the tight regulation of mucin overproduction in the pathogenesis of airway infectious diseases and may lead to development of new therapeutic strategies...
  98. ncbi Natural development of antibodies to pneumococcal surface protein A, pneumococcal surface adhesin A, and pneumolysin in relation to pneumococcal carriage and acute otitis media
    S Rapola
    National Public Health Institute, Dept of Vaccines, 00300 Helsinki, Finland
    J Infect Dis 182:1146-52. 2000
    ..All age groups were capable of producing antibodies to the 3 proteins. The antibody concentrations increased with age and were strongly associated with pneumococcal exposure, whether by carriage or infection (acute otitis media)...
  99. pmc Bacterial programmed cell death of cerebral endothelial cells involves dual death pathways
    Daniela Bermpohl
    Department of Neurology, Center of Anatomy, Charite Universitatsmedizin Berlin, Berlin, Germany
    J Clin Invest 115:1607-15. 2005
    ..These findings broaden the scope of bacterial-induced PCD, link these effects to innate immune TLRs, and provide insight into the acute and persistent phases of damage during meningitis...
  100. pmc Host and bacterial factors contributing to the clearance of colonization by Streptococcus pneumoniae in a murine model
    Annemarie M C van Rossum
    University of Pennsylvania, 402A Johnson Pavilion, Philadelphia, PA 19104 6076, USA
    Infect Immun 73:7718-26. 2005
    ..We conclude that both innate and CD4+ T-cell-mediated immunity and proinflammatory bacterial factors, rather than a humoral adaptive immune response, are important for clearance of S. pneumoniae from the murine nasopharynx...
  101. pmc Dual function of pneumolysin in the early pathogenesis of murine pneumococcal pneumonia
    J B Rubins
    Pulmonary Disease Division, Veterans Affairs Medical Center, Minneapolis, Minnesota
    J Clin Invest 95:142-50. 1995
    ..Moreover, both the cytotoxic and the complement-activating activities of pneumolysin may contribute independently to the acute pulmonary injury and the high rates of bacteremia which characterize pneumococcal pneumonia...

Research Grants45

  1. A common denominator of pathogenesis;a rare opportunity for novel therapeutic de
    DOUGLAS ALAN MITCHELL; Fiscal Year: 2011
    ..A greater understanding of these processes will lay the foundation for developing the next generation of antimicrobial drugs. ..
  2. Cardiac dysfunction in StrepTSS: interplay of SLO and MMPs
    Dennis L Stevens; Fiscal Year: 2013
    ....
  3. Single RNA sensitive probes for studying viral replication and budding
    Philip J Santangelo; Fiscal Year: 2013
    ....
  4. Host-pathogen signaling in group A streptococcal infection
    Michael R Wessels; Fiscal Year: 2012
    ..Understanding this process may lead to new strategies for prevention or treatment of GAS infection. ..
  5. CYTOLYSIN-MEDIATED TRANSLOCATION IN S. PYOGENES VIRULENC
    Michael G Caparon; Fiscal Year: 2013
    ..This information will be important for understanding how the multiple toxins of S. pyogenes interact with each other and with host cells to unravel how this pathogen can cause such a diverse range of different diseases. ..
  6. Pore Formation by Cholesterol Dependent Cytolysins
    Rodney K Tweten; Fiscal Year: 2013
    ....
  7. Vaccine and therapeutic antibodies against Group A Streptococcus
    Benfang Lei; Fiscal Year: 2013
    ..The project has the potential to lead to the development of a broad vaccine against GAS diseases and an antibody therapy to treat severe GAS infections. ..
  8. Design and Use of Novel Bacteriocins
    Shaun Lee; Fiscal Year: 2011
    ..This proposal presents a method of generating an entirely new class of antibiotic compounds, many of which will undoubtedly have tremendous public health value. ..
  9. Evasion of Innate Immunity by Group A Streptococcus
    Benfang Lei; Fiscal Year: 2013
    ..Overall, this project has the potential to define a novel mechanism for evasion of innate immunity by GAS and to establish a paradigm for bacterial inhibition of neutrophil recruitment and function. ..
  10. HETEROTRIMERIC G PROTEINS AND EXOCYTOSIS
    BHANU JENA; Fiscal Year: 1999
    ..Understanding the role of the secretory granule membrane-associated G-proteins in exocytosis will help us understand better this fundamental cellular process which when impaired leads to a number of diseases. ..
  11. FUNCTION OF A BRAIN CALCIUM-BINDING PROTEIN
    DONALD WOLFF; Fiscal Year: 1991
    ..We propose to purify this phosphatase by immunoaffinity chromatography and to compare its physical, kinetic and chemical properties with the bovine brain homolog...
  12. REGULATION OF EXOCYTOSIS IN MAST CELLS
    J Castle; Fiscal Year: 2004
    ..abstract_text> ..
  13. MUCOID VARIANTS OF S PYOGENES EXHIBIT ENHANCED VIRULENCE
    N Engleberg; Fiscal Year: 2001
    ..If so, this observation will have major impact on the future analyses of human cases. ..
  14. STREPTOCOCCUS PYOGENES--CLONAL ANALYSIS OF VIRULENCE
    Edward Graviss; Fiscal Year: 2000
    ..The P.I. also proposes to explore in depth his own finding, recently published, that SpeB cleaves and activates a matrix metallo-protease produced by human endothelial cells. ..
  15. P56C2, A NOVEL C2 DOMAIN PROTEIN OF LEUKOCYTES
    BERNARD BABIOR; Fiscal Year: 2003
    ..abstract_text> ..
  16. CONTROL OF AUTOLYSIS IN PNEUMOCOCCI
    Elaine Tuomanen; Fiscal Year: 2006
    ..abstract_text> ..
  17. SLS: Molecular Basis and Role in Invasive GAS Disease
    Victor Nizet; Fiscal Year: 2006
    ..These hypotheses will be tested by molecular genetic studies, attempts protein purification and antibody development, and the use of targeted SLS mutants in in vitro assays of phagocytic function and our in vivo mouse model of GAS NF. ..
  18. Sialic Acid O-Acetylation in GBS Pathogenesis & Immunity
    Victor Nizet; Fiscal Year: 2010
    ..Companion analyses will be performed on GBS isolates and human sera from recent prospective seroepidemiologic studies. ..
  19. MOLECULAR AND CELLULAR BACTERIAL PATHOGENESIS
    David Briles; Fiscal Year: 2008
    ..The MCBP advisory committee will advise the trainees in their research and training programs and in their search for a job or postdoctoral position at the completion of their MCBP training. [unreadable] [unreadable]..
  20. DEFENSINS--ANTIMICROBIAL PEPTIDES OF HUMAN NEUTROPHILS
    Robert Lehrer; Fiscal Year: 2002
    ..The work with murine neutrophils, whose content of endogenous antimicrobial polypeptides differs greatly from those of humans, will provide essential information relevant to the interpretation of murine models of human infection. ..
  21. Chemical Genetic Analysis of Platelet Granule Secretion
    Robert Flaumenhaft; Fiscal Year: 2008
    ..Once identified, compounds will be tested in a previously established battery of platelet function tests and evaluated for antithrombotic potential in an in vivo murine model of thrombus formation. [unreadable] [unreadable] [unreadable]..
  22. ALTRUINS, NATURAL ANTIBIOTICS OF THE MALE GENITAL TRACT
    Robert Lehrer; Fiscal Year: 2001
    ..S. are sexually transmitted. According to CDC estimates, STDs other than AIDS add 10 billion dollars to the nation's annual health care I costs. The proposed studies could lead to novel approaches for STD prophylaxis. ..
  23. MACROMOLECULAR ARRAYS IN EXTRACELLULAR MATRIX OF COCHLEA
    Vladimir Tsuprun; Fiscal Year: 2003
    ..Methods of structural crystallography, Fourier (Fast Fourier Transformation) image analysis of periodic objects, and computer averaging to obtain enhanced, noise-free images will be applied in this study. ..
  24. Retrocyclins: Cyclic mini-defensins that inactivate anthrax toxins
    ROBERT IRVING contact LEHRER; Fiscal Year: 2010
    ..anthracis spores in mouse models as per the revised Specific Aims. All remaining Aims can be addressed in a two-year time period. PHS ..
  25. STRUCTURAL STUDIES OF BACTERIAL HYALURONATE LYASE ENZYME
    MARK JEDRZEJAS; Fiscal Year: 2003
    ..The results will enhance our knowledge about mechanisms involved in the action of the enzyme and in the pathogenesis of S. pneumoniae bacteria. ..
  26. STRUCTURE/FUNCTIONS OF HUMAN TEAR LIPOPHILIN
    Robert Lehrer; Fiscal Year: 2001
    ..The long-term objectives for this research are to learn how lipophilin contributes to corneal and conjuctival health, and to explore its potential for creating new diagnostic and therapeutic modalities. ..
  27. MHC CLASS I ANTIGEN PROCESSING AND PRESENTATION
    Matthew Androlewicz; Fiscal Year: 2001
    ..abstract_text> ..
  28. SNARE HYPOTHESIS AT NERVE ENDINGS
    EDWARD STUENKEL; Fiscal Year: 2002
    ..In summary, an understanding of the mechanisms by which nSec1p regulates SNARE protein interactions may be essential to full understanding of both short and long-term processes of synaptic plasticity and memory. ..
  29. NEUTROPHIL RECRUITMENT IN LPS-INDUCED AIRWAY DISEASE
    Jessica Moreland; Fiscal Year: 2004
    ....
  30. Biacore 3000 SPR Instrument
    Robert Lehrer; Fiscal Year: 2004
    ..These include the development of new agents and approaches to prevent and treat infections caused by HIV-1 and other viral pathogens, and fundamental issues related to cell targeting and survival. ..
  31. Polymicrobial induction of epithelial inflammation
    Adam Ratner; Fiscal Year: 2008
    ..Ratner to a wide variety of techniques in the areas of cell biology, biochemistry, physiology, and molecular biology, thus providing a solid foundation for beginning an independent research career. [unreadable] [unreadable] [unreadable]..
  32. AIRWAY SMOOTH MUSCLE IN HEALTH AND DISEASE
    RONALD COBURN; Fiscal Year: 2004
    ..In particular, all of these diseases cause physiological alterations that influence the length at which smooth muscle cells contract and relax. ..
  33. Role of Racl in Regulated Exocytosis
    EDWARD STUENKEL; Fiscal Year: 2004
    ..The work proposed attempts to provide a greater understanding of cytosolic and membrane delimited signaling pathways that exert an important regulatory influence on Ca2+- dependent secretory responsiveness. ..
  34. Air Quality Improvements of The Animal Facility
    Michael Gilmore; Fiscal Year: 2005
    ..This will significantly improve the quality of vision research conducted by the Faculty at the Schepens. ..
  35. Resistant Enterococci in the GI tract Consortium
    Michael Gilmore; Fiscal Year: 2004
    ..Based on these results, well-grounded specific questions can be postulated and tested subsequently to verify their importance in vivo, ultimately leading to the design of agents to prevent colonization by antibiotic resistant strains. ..
  36. ORAL BIOFILMS: DIFFERENTIAL DISPLAY AND GENETIC EXCHANGE
    Michael Gilmore; Fiscal Year: 2003
    ..abstract_text> ..
  37. ALPHA HELICAL CATHELICIDINS AND HOST DEFENSE
    Robert Lehrer; Fiscal Year: 2003
    ..The experiments will expand our knowledge about these important peptides, and should provide the information needed to develop them as antibiotics for topical bronchopulmonary use in cystic fibrosis. ..
  38. Drosophila model of antibiotic resistant infection
    Michael Gilmore; Fiscal Year: 2006
    ..abstract_text> ..
  39. SNARE PROTEINS IN PLATELET ALPHA-GRANULE SECRETION
    Robert Flaumenhaft; Fiscal Year: 2007
    ..abstract_text> ..
  40. Theta-defensins Novel HIV-1 Uptake Inhibitors
    Robert Lehrer; Fiscal Year: 2007
    ..Specific Aim 2 will be realized by a combination of microchemical techniques, including surface plasmon resonance, tandem mass spectrometry, and state-of-the-art lectinomic and peptidomic chemistry. ..
  41. Retrocyclin reinforcement of pulmonary defenses against viral aerosols
    Robert Lehrer; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  42. Role of CIC-3 channels in regulation of cell volume and shape in neutrophils
    Jessica Moreland; Fiscal Year: 2007
    ..The studies proposed will advance our fundamental knowledge of the function of neutrophils in the maintenance of normal immune system function. [unreadable] [unreadable] [unreadable]..
  43. Regulation of tomosyn-SNARE complex assembly in neurosecretion
    Edward L Stuenkel; Fiscal Year: 2010
    ....