The pathogenic gram-positive bacterium Streptococcus pyogenes (group A streptococcus) causes numerous diseases of cutaneous tissue, each of which is initiated after the interaction of the bacterium with the cells of the epidermis. In this study, we show that different surface proteins of S. pyogenes play important roles in determining the cell-specific tropism of the bacterium in skin. Using streptococcal strains with defined mutations in the genes which encode surface proteins in combination with primary cultures of human skin and an in situ adherence assay which uses histological sections of human skin, we show that the M protein of S. pyogenes mediates the binding of the bacterium to keratinocytes, while a second streptococcal surface protein, protein F, directs the adherence of the organism to Langerhans' cells. Characterization of binding revealed that adherence was inhibited by purified streptococcal proteins and pretreatment of both host cells with the protease trypsin. Adherence was only slightly affected by the state of keratinocyte differentiation in vitro, but was considerably modulated in response to environmental conditions known to regulate expression of M protein and protein F, suggesting that the interaction between these bacterial cell-surface structures/adhesins and keratinocytes and Langerhans' cells may play an important role in streptococcal skin disease.
N Okada, A P Pentland, P Falk, M G Caparon
Title and authors | Publication | Year |
---|---|---|
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Streptococcal pharyngitis and rheumatic heart disease: the superantigen hypothesis revisited
JR Hurst, KJ Kasper, AN Sule, JK McCormick |
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases | 2018 |
Immunization with a streptococcal multiple-epitope recombinant protein protects mice against invasive group A streptococcal infection
CF Kuo, N Tsao, IC Hsieh, YS Lin, JJ Wu, YT Hung, PL Ho |
PloS one | 2017 |
Superoxide anions produced by Streptococcus pyogenes group A-stimulated keratinocytes are responsible for cellular necrosis and bacterial growth inhibition
E Regnier, PA Grange, G Ollagnier, E Crickx, L Elie, S Chouzenoux, B Weill, C Plainvert, C Poyart, F Batteux, N Dupin |
Innate immunity | 2016 |
A comprehensive analysis of the Streptococcus pyogenes and human plasma protein interaction network
K Sjöholm, C Karlsson, A Linder, J Malmström |
Molecular BioSystems | 2014 |
Host-Pathogen Interactions in Streptococcal Diseases
GS Chhatwal |
2012 | |
Host-Pathogen Interactions in Streptococcal Diseases
GS Chhatwal |
2012 | |
Host-Pathogen Interactions in Streptococcal Diseases
GS Chhatwal |
2012 | |
Host-Pathogen Interactions in Streptococcal Diseases
GS Chhatwal |
2012 | |
Host-Pathogen Interactions in Streptococcal Diseases
GS Chhatwal |
2012 | |
Host-Pathogen Interactions in Streptococcal Diseases
GS Chhatwal |
2012 | |
Host-Pathogen Interactions in Streptococcal Diseases
GS Chhatwal |
2012 | |
Current insights in invasive group A streptococcal infections in pediatrics
A Filleron, E Jeziorski, AL Michon, M Rodière, H Marchandin |
European Journal of Pediatrics | 2012 |
Methods in Enzymology
JD Stone, AS Chervin, DH Aggen, DM Kranz |
Protein Engineering for Therapeutics Part B | 2012 |
The Membrane Bound LRR Lipoprotein Slr, and the Cell Wall-Anchored M1 Protein from Streptococcus pyogenes Both Interact with Type I Collagen
M Bober, M Mörgelin, AI Olin, U Pawel-Rammingen, M Collin, S Bereswill |
PloS one | 2011 |
Streptococcus pyogenes M49 Plasminogen/Plasmin Binding Facilitates Keratinocyte Invasion via Integrin-Integrin-linked Kinase (ILK) Pathways and Protects from Macrophage Killing*
N Siemens, N Patenge, J Otto, T Fiedler, B Kreikemeyer |
The Journal of biological chemistry | 2011 |
A CD46 transgenic mouse model for studying the histopathology of arthritis caused by subcutaneous infection with Streptococcus dysgalactiae subspecies equisimilis
H Yoshida, H Matsui, SY Murayama, Y Takada, K Matsuo, T Takahashi, M Nakamura, K Ubukata, T Takahashi |
Journal of Medical Microbiology | 2011 |
Streptococcus pyogenes M49 Plasminogen/Plasmin Binding Facilitates Keratinocyte Invasion via Integrin-Integrin-linked Kinase (ILK) Pathways and Protects from Macrophage Killing
N Siemens, N Patenge, J Otto, T Fiedler, B Kreikemeyer |
The Journal of biological chemistry | 2011 |
Tissue tropisms in group A streptococcal infections
DE Bessen, S Lizano |
Future Microbiology | 2010 |
Cellular interactions by LPxTG-anchored pneumococcal adhesins and their streptococcal homologues
J Löfling, V Vimberg, P Battig, B Henriques-Normark |
Cellular Microbiology | 2010 |
The streptococcal M protein: a highly versatile molecule
PR Smeesters, DJ McMillan, KS Sriprakash |
Trends in Microbiology | 2010 |
Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases
VG Fowler, WM Scheld, AS Bayer |
Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases | 2010 |
Moving forward: a mucosal vaccine against group A streptococcus
MM Georgousakis, DJ McMillan, MR Batzloff, KS Sriprakash |
Expert Review of Vaccines | 2009 |
Positive correlation between low adhesion of group A Streptococcus to mammalian cells and virulence in a mouse model
T Miyoshi-Akiyama, J Zhao, T Uchiyama, J Yagi, T Kirikae |
FEMS Microbiology Letters | 2009 |
Streptolysin S Inhibits Neutrophil Recruitment during the Early Stages of Streptococcus pyogenes Infection
A Lin, JA Loughman, BH Zinselmeyer, MJ Miller, MG Caparon |
Infection and immunity | 2009 |
Hot Topics in Infection and Immunity in Children IV
A Finn, AJ Pollard |
2008 | |
Hot Topics in Infection and Immunity in Children IV
A Finn, AJ Pollard |
2008 | |
Hot Topics in Infection and Immunity in Children IV
A Finn, AJ Pollard |
2008 | |
Streptococcus iniae M-Like Protein Contributes to Virulence in Fish and Is a Target for Live Attenuated Vaccine Development
JB Locke, RK Aziz, MR Vicknair, V Nizet, JT Buchanan, N Ahmed |
PloS one | 2008 |
Group A streptococcus cell-associated pathogenic proteins as revealed by growth in hyaluronic acid-enriched media
M Zhang, FM McDonald, SS Sturrock, SJ Charnock, I Humphery-Smith, GW Black |
PROTEOMICS | 2007 |
RivR and the small RNA RivX: the missing links between the CovR regulatory cascade and the Mga regulon
SA Roberts, JR Scott |
Molecular Microbiology | 2007 |
Pili mediate specific adhesion of Streptococcus pyogenes to human tonsil and skin
EL Abbot, WD Smith, GP Siou, C Chiriboga, RJ Smith, JA Wilson, BH Hirst, MA Kehoe |
Cellular Microbiology | 2007 |
Mesenchymal stem cells and tissue engineering
NW Marion, JJ Mao |
Methods in enzymology | 2006 |
The Prokaryotes
M Dworkin, S Falkow, E Rosenberg, KH Schleifer, E Stackebrandt |
2006 | |
Colonization of Mucosal Surfaces
JP Nataro, PS Cohen, HL Mobley, JN Weiser |
2005 | |
Identification of Group A Streptococcus Antigenic Determinants Upregulated In Vivo
KY Salim, DG Cvitkovitch, P Chang, DJ Bast, M Handfield, JD Hillman, JC de Azavedo |
Infection and immunity | 2005 |
The Streptococcus pyogenes capsule is required for adhesion of bacteria to virus-infected alveolar epithelial cells and lethal bacterial-viral superinfection
S Okamoto, S Kawabata, Y Terao, H Fujitaka, Y Okuno, S Hamada |
Infection and immunity | 2004 |
Fibronectin-binding protein gene recombination and horizontal transfer between group A and G streptococci
RJ Towers, D Gal, D McMillan, KS Sriprakash, BJ Currie, MJ Walker, GS Chhatwal, PK Fagan |
Journal of clinical microbiology | 2004 |
Bacterial Invasion of Host Cells
RJ Lamont |
2004 | |
Role of M3 protein in the adherence and internalization of an invasiveStreptococcus pyogenesstrain by epithelial cells
O Eyal, J Jadoun, A Bitler, E Skutelski, S Sela |
FEMS Immunology & Medical Microbiology | 2003 |
Molecular basis of group A streptococcal virulence
AL Bisno, MO Brito, CM Collins |
The Lancet Infectious Diseases | 2003 |
Site-specific manifestations of invasive group a streptococcal disease: type distribution and corresponding patterns of virulence determinants
BJ Vlaminckx, EM Mascini, J Schellekens, LM Schouls, A Paauw, AC Fluit, R Novak, J Verhoef, FJ Schmitz |
Journal of clinical microbiology | 2003 |
Bacterial Adhesion to Animal Cells and Tissues
I Ofek, DL Hasty, RJ Doyle |
2003 | |
Evolution of sfbI Encoding Streptococcal Fibronectin-Binding Protein I: Horizontal Genetic Transfer and Gene Mosaic Structure
RJ Towers, PK Fagan, SR Talay, BJ Currie, KS Sriprakash, MJ Walker, GS Chhatwal |
Journal of clinical microbiology | 2003 |
Methods in Cell Biology
JW Smith |
Methods in cell biology | 2002 |
Expression of the Biofilm-Associated Protein Interferes with Host Protein Receptors of Staphylococcus aureus and Alters the Infective Process
C Cucarella, MA Tormo, E Knecht, B Amorena, I Lasa, TJ Foster, JR Penadés |
Infection and immunity | 2002 |
Identification of the Streptococcal M Protein Binding Site on Membrane Cofactor Protein (CD46)
E Giannakis, TS Jokiranta, RJ Ormsby, TG Duthy, DA Male, D Christiansen, VA Fischetti, C Bagley, BE Loveland, DL Gordon |
Journal of immunology (Baltimore, Md. : 1950) | 2002 |
The role played by the group A streptococcal negative regulator Nra on bacterial interactions with epithelial cells
G Molinari, M Rohde, SR Talay, GS Chhatwal, S Beckert, A Podbielski |
Molecular Microbiology | 2001 |
Bacterial determinants of persistent throat colonization and the associated immune response in a primate model of human group A streptococcal pharyngeal infection
CD Ashbaugh, TJ Moser, MH Shearer, GL White, RC Kennedy, MR Wessels |
Cellular Microbiology | 2001 |
De novo formation of focal complex-like structures in host cells by invading Streptococci
V Ozeri, I Rosenshine, A Ben-Ze'Ev, GM Bokoch, TS Jou, E Hanski |
Molecular Microbiology | 2001 |
Isolation of human plasma-inducible, growth phase- and temperature-regulated gene fusions in Streptococcus pyogenes using a Tn917–lacZ transposon
DD Sledjeski, C Coco, C Corriher, MD Boyle |
Journal of Microbiological Methods | 2001 |
Principles of Bacterial Pathogenesis
M Caparon |
Principles of Bacterial Pathogenesis | 2001 |
Restoration of Mga Function to a Streptococcus pyogenes Strain (M Type 50) That Is Virulent in Mice
JT Barbieri, B Limbago, KS McIver, V Penumalli, B Weinrick, JR Scott |
Infection and immunity | 2001 |
Pathogenesis of group A streptococcal infections
MW Cunningham |
Clinical microbiology reviews | 2000 |
A nonpeptide integrin antagonist can inhibit epithelial cell ingestion of Streptococcus pyogenes by blocking formation of integrin alpha 5beta 1-fibronectin-M1 protein complexes
D Cue, SO Southern, PJ Southern, J Prabhakar, W Lorelli, JM Smallheer, SA Mousa, PP Cleary |
Proceedings of the National Academy of Sciences | 2000 |
A nonpeptide integrin antagonist can inhibit epithelial cell ingestion of Streptococcus pyogenes by blocking formation of integrin alpha 5 beta 1-fibronectin-M1 protein complexes
D Cue, SO Southern, PJ Southern, J Prabhakar, W Lorelli, JM Smallheer, SA Mousa, PP Cleary |
Proceedings of the National Academy of Sciences | 2000 |
Dermo-hypodermites nécrosantes: données microbiologiques et pathogéniques
A Bouvet |
Médecine et Maladies Infectieuses | 2000 |
Bacterial Invasion into Eukaryotic Cells
TA Oelschlaeger, J Hacker |
2000 | |
Role of Group A Streptococcal Virulence Factors in Adherence to Keratinocytes
EI Tuomanen, GL Darmstadt, L Mentele, A Podbielski, CE Rubens |
Infection and immunity | 2000 |
Synthetic Peptide Immunogens Elicit Polyclonal and Monoclonal Antibodies Specific for Linear Epitopes in the D Motifs of Staphylococcus aureus Fibronectin-Binding Protein, Which Are Composed of Amino Acids That Are Essential for Fibronectin Binding
EI Tuomanen, M Huesca, Q Sun, R Peralta, GM Shivji, DN Sauder, MJ McGavin |
Infection and immunity | 2000 |
Absence of SpeB Production in Virulent Large Capsular Forms of Group A Streptococcal Strain 64
EI Tuomanen, R Raeder, E Harokopakis, S Hollingshead, MD Boyle |
Infection and immunity | 2000 |
The RofA Binding Site in Streptococcus pyogenes Is Utilized in Multiple Transcriptional Pathways
AB Granok, D Parsonage, RP Ross, MG Caparon |
Journal of bacteriology | 2000 |
Human Dendritic Cells Are Superior to B Cells at Presenting a Major Histocompatibility Complex Class II-Restricted Heterologous Antigen Expressed on Recombinant Streptococcus gordonii
JT Barbieri, S Corinti, D Medaglini, C Prezzi, A Cavani, G Pozzi, G Girolomoni |
Infection and immunity | 2000 |
Characterization of nra, a global negative regulator gene in group A streptococci
A Podbielski, M Woischnik, BA Leonard, KH Schmidt |
Molecular Microbiology | 1999 |
Expression of different group A streptococcal M proteins in an isogenic background demonstrates diversity in adherence to and invasion of eukaryotic cells
C Berkower, M Ravins, AE Moses, E Hanski |
Molecular Microbiology | 1999 |
The R28 protein of Streptococcus pyogenes is related to several group B streptococcal surface proteins, confers protective immunity and promotes binding to human epithelial cells
M Stålhammar-Carlemalm, T Areschoug, C Larsson, G Lindahl |
Molecular Microbiology | 1999 |
Streptococcal invasion
G Molinari, GS Chhatwal |
Current Opinion in Microbiology | 1999 |
Surface proteins of gram-positive bacteria and mechanisms of their targeting to the cell wall envelope
WW Navarre, O Schneewind |
Microbiology and molecular biology reviews : MMBR | 1999 |
Capsular hyaluronic acid of Group A Streptococci hampers their invasion into human pharyngeal epithelial cells
S Kawabata, H Kuwata, I Nakagawa, S Morimatsu, K Sano, S Hamada |
Microbial Pathogenesis | 1999 |
Immunsystem und Infektiologie
D Ganten, K Ruckpaul |
1999 | |
A Response Regulator That Represses Transcription of Several Virulence Operons in the Group A Streptococcus
MJ Federle, KS McIver, JR Scott |
Journal of bacteriology | 1999 |
Identification of pel , a Streptococcus pyogenes Locus That Affects both Surface and Secreted Proteins
Z Li, DD Sledjeski, B Kreikemeyer, A Podbielski, MD Boyle |
Journal of bacteriology | 1999 |
Hyaluronic acid capsule modulates M protein-mediated adherence and acts as a ligand for attachment of group A Streptococcus to CD44 on human keratinocytes
HM Schrager, S Albertí, C Cywes, GJ Dougherty, MR Wessels |
Journal of Clinical Investigation | 1998 |
Differentiation of cultured keratinocytes promotes the adherence of Streptococcus pyogenes
GL Darmstadt, P Fleckman, M Jonas, E Chi, CE Rubens |
Journal of Clinical Investigation | 1998 |
New targets for antibiotic development: biogenesis of surface adherence structures
CH Jones, DE Hruby |
Drug Discovery Today | 1998 |
High-frequency intracellular infection and erythrogenic toxin A expression undergo phase variation in M1 group A streptococci
PP Cleary, L McLandsborough, L Ikeda, D Cue, J Krawczak, H Lam |
Molecular Microbiology | 1998 |
Roles of integrins and fibronectin in the entry of Streptococcus pyogenes into cells via protein F1
V Ozeri, I Rosenshine, DF Mosher, R Fassler, E Hanski |
Molecular Microbiology | 1998 |
Prevalence of internalisation-associated gene, prtF1, among persisting group-A streptococcus strains isolated from asymptomatic carriers
R Neeman, N Keller, A Barzilai, Z Korenman, S Sela |
The Lancet | 1998 |
Immunoglobulins to group A streptococcal surface molecules decrease adherence to and invasion of human pharyngeal cells
U Fluckiger, KF Jones, VA Fischetti |
Infection and immunity | 1998 |
Protein F, a fibronectin-binding protein of Streptococcus pyogenes, also binds human fibrinogen: isolation of the protein and mapping of the binding region
V Katerov, A Andreev, C Schalén, AA Totolian |
Microbiology | 1998 |
Streptococcus pyogenes protein F promotes invasion of HeLa cells
N Okada, lchiro Tatsuno, E Hanski, M Caparon, C Sasakawa |
Microbiology | 1998 |
Streptococcus pyogenes Serotype M1 Encodes Multiple Pathways for Entry into Human Epithelial Cells
PE Orndorff, D Cue, PE Dombek, H Lam, PP Cleary |
Infection and immunity | 1998 |
M protein mediated adhesion of M type 24 Streptococcus pyogenes stimulates release of interleukin-6 by HEp-2 tissue culture cells
HS Courtney, I Ofek, DL Hasty |
FEMS Microbiology Letters | 1997 |
The fibronectin-binding protein of Streptococcus pyogenes, SfbI, is involved in the internalization of group A streptococci by epithelial cells
G Molinari, SR Talay, P Valentin-Weigand, M Rohde, GS Chhatwal |
Infection and immunity | 1997 |
Constitutive expression of fibronectin binding in Streptococcus pyogenes as a result of anaerobic activation of rofA
GC Fogg, MG Caparon |
Journal of bacteriology | 1997 |
Keratinocyte proinflammatory responses to adherent and nonadherent group A streptococci
B Wang, N Ruiz, A Pentland, M Caparon |
Infection and immunity | 1997 |
Identification of D motif epitopes in Staphylococcus aureus fibronectin-binding protein for the production of antibody inhibitors of fibronectin binding
Q Sun, GM Smith, C Zahradka, MJ McGavin |
Infection and immunity | 1997 |
Efficient insertional mutagenesis in group A streptococci mediated by Tn917 transposon
Z Li, JA Gutierrez, AS Bleiweis, MD Boyle |
Journal of Microbiological Methods | 1997 |
A Matrix Form of Fibronectin Mediates Enhanced Binding of Streptococcus pyogenes to Host Tissue
N Okada, M Watarai, V Ozeri, E Hanski, M Caparon, C Sasakawa |
The Journal of biological chemistry | 1997 |
Emerging Infections 1
WM Scheld, D Armstrong, JM Hughes |
1997 | |
Biological properties of a Streptococcus pyogenes mutant generated by Tn916 insertion in mga
BM Kihlberg, J Cooney, MG Caparon, A Olsén, L Björck |
Microbial Pathogenesis | 1996 |
An oxygen-induced but protein F-independent fibronectin-binding pathway in Streptococcus pyogenes
JY Lee, M Caparon |
Infection and immunity | 1996 |
The hemagglutinin of Staphylococcus saprophyticus is a major adhesin for uroepithelial cells
HG Meyer, U Wengler-Becker, SG Gatermann |
Infection and immunity | 1996 |
Identification of a fibronectin-binding protein (GfbA) in pathogenic group G streptococci
JB Kline, S Xu, AL Bisno, CM Collins |
Infection and immunity | 1996 |
Infections sévères dues à Streptococcus pyogenes ou streptocoque du groupe A
A Bouvet |
Médecine et Maladies Infectieuses | 1996 |
Toward Anti-Adhesion Therapy for Microbial Diseases
I Kahane, I Ofek |
1996 | |
Role of the conserved C-repeat region of the M protein of Streptococcus pyogenes
J Perez-Casal, N Okada, MG Caparon, JR Scott |
Molecular Microbiology | 1995 |
Membrane cofactor protein (CD46) is a keratinocyte receptor for the M protein of the group A streptococcus
N Okada, MK Liszewski, JP Atkinson, M Caparon |
Proceedings of the National Academy of Sciences | 1995 |
Molecular Aspects of Bacterial Colonization
AL Bisno |
Infection Control and Hospital Epidemiology | 1995 |