The human IgA-Fc α receptor interaction and its blockade by streptococcal IgA-binding proteins

2002 ◽  
Vol 30 (4) ◽  
pp. 491-494 ◽  
Author(s):  
J. M. Woof
Keyword(s):  
Pathogenic Bacteria ◽  
Surface Proteins ◽  
Receptor Interaction ◽  
Group B Streptococci ◽  
Domain Swap ◽  
Mucosal Surfaces ◽  
Β Protein ◽  
Group B ◽  
A Site ◽  
Streptococcal Proteins

IgA plays a key role in immune defence of the mucosal surfaces. IgA can trigger elimination mechanisms against pathogens through the interaction of its Fc region with FcαRs (receptors specific for the Fc region of IgA) present on neutrophils, macrophages, monocytes and eosinophils. The human FcαR (CD89) shares homology with receptors specific for the Fc region of IgG (FcαRs) and IgE (FcαRIs), but is a more distantly related member of the receptor family. CD89 interacts with residues lying at the interface of the two domains of IgA Fc, a site quite distinct from the homologous regions at the top of IgG and IgE Fc recognized by FcαR and FcαRI respectively. Certain pathogenic bacteria express surface proteins that bind to human IgA Fc. Experiments with domain-swap antibodies and mutant IgAs indicate that binding of three such proteins (Sir22 and Arp4 of Streptococcus pyogenes and β protein of group B streptococci) depend on sites in the Fc interdomain region of IgA, the binding region also used by CD89. Further, we have found that the streptococcal proteins can inhibit interaction of IgA with CD89, and have thereby identified a mechanism by which a bacterial IgA-binding protein may modulate IgA effector function.

scholarly journals M1 protein and protein H: IgGFc- and albumin-binding streptococcal surface proteins encoded by adjacent genes

1994 ◽  
Vol 300 (3) ◽  
pp. 877-886 ◽  
Author(s):  
P Åkesson ◽  
K H Schmidt ◽  
J Cooney ◽  
L Björck
Keyword(s):  
Mhc Class Ii ◽  
Pathogenic Bacteria ◽  
Mammalian Species ◽  
Class Ii ◽  
Surface Proteins ◽  
Significant Similarity ◽  
M1 Protein ◽  
Beta 2 Microglobulin ◽  
Class Ii Antigens ◽  
Streptococcal Proteins

M1 protein and Protein H are surface proteins simultaneously present at the surface of certain strains of Streptococcus pyogenes, important pathogenic bacteria in humans. The present study concerns the structure, protein-binding properties and relationship between these two molecules. The gene encoding M1 protein (emm1) was found immediately upstream of the Protein H gene (sph). Both genes were preceded by a promoter region. Comparison of the sequences revealed a high degree of similarity in the signal peptides, the C repeats located in the central parts of the molecules and in the C-terminal cell-wall-attached regions, whereas the N-terminal sequences showed no significant similarity. Protein H has affinity for the Fc region of IgG antibodies. Also M1 protein, isolated from streptococcal culture supernatants or from Escherichia coli expressing emm1, was found to bind human IgGFc. When tested against polyclonal IgG from eight other mammalian species, M1 protein and Protein H both showed affinity for baboon, rabbit and pig IgG. M1 protein also reacted with guinea-pig IgG, whereas both streptococcal proteins were negative in binding experiments with rat, mouse, bovine and horse IgG. The two proteins were also tested against other members of the immunoglobulin super family: human IgM, IgA, IgD, IgE, beta 2-microglobulin, and major histocompatibility complex (MHC) class-I and class-II antigens. M1 protein showed no affinity for any of these molecules whereas Protein H reacted with MHC class-II antigens. M1 protein is known to bind albumin and fibrinogen also. The binding sites for these two plasma proteins and for IgGFc were mapped to different sites on M1 protein. Thus albumin bound to the C repeats and IgGFc to a region (S) immediately N-terminal of the C repeats. Finally, fibrinogen bound further towards the N-terminus but close to the IgGFc-binding site. On the fibrinogen molecule, fragment D was found to mediate binding to M1 protein. The IgGFc-binding region of M1 protein showed no similarity to that of Protein H. Still, competitive binding experiments demonstrated that the two streptococcal proteins bound to overlapping sites on IgGFc.

scholarly journals Interaction between Pathogenic Bacteria and Intrauterine Leukocytes Triggers Alternative Molecular Signaling Cascades Leading to Labor in Women

2010 ◽  
Vol 78 (11) ◽  
pp. 4792-4799 ◽  
Author(s):  
Guadalupe Estrada-Gutierrez ◽  
Nardhy Gomez-Lopez ◽  
Veronica Zaga-Clavellina ◽  
Silvia Giono-Cerezo ◽  
Aurora Espejel-Nuñez ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Preterm Labor ◽  
Pathogenic Bacteria ◽  
Prostaglandin E ◽  
Molecular Signaling ◽  
Group B Streptococci ◽  
Increased Risk ◽  
Tnf Α ◽  
Human Labor ◽  
Group B

ABSTRACT Increased risk of preterm labor has been linked to cervicovaginal infection with Ureaplasma urealyticum and group B streptococci. Although various experimental models have been developed to study the role of amniochorion infection in preterm labor, they typically exclude the initial interaction between intrauterine leukocytes (recruited from decidual vessels into the avascular fetal membranes) and infecting bacteria. In this work, we ascertained whether inflammatory molecules secreted by bacterium-activated intrauterine leukocytes stimulate the amniochorion production of mediators involved in human labor. Using a two-step process beginning with placental circulating leukocytes as a proxy for intrauterine leukocytes, we found that coincubation of amniochorion explants with plasma from placental whole blood preincubated with group B streptococci resulted in a significant increase in tumor necrosis factor alpha (TNF-α) and matrix metalloproteinase 9 (MMP-9) levels in tissue. Extensive changes in the connective tissue arrangement and a decrease in collagen content demonstrated the degradation of the extracellular matrix following this treatment. In contrast, plasma from blood preconditioned with U. urealyticum induced a highly significant secretion of interleukin-1β (IL-1β) and prostaglandin E2 (PGE2) by the amniochorion without changes in the extracellular matrix organization or content. These data demonstrate that group B streptococci induce degradation of the amniochorion as a result of MMP-9 production, probably via TNF-α, whereas U. urealyticum stimulates the secretion of PGE2, probably via IL-1β, potentially stimulating myometrial contraction. Our study provides novel evidence that the immunological cells circulating within the uterine microenvironment respond differentially to an infectious agent, triggering alternative molecular signaling pathways leading to human labor.

Immunoglobulins and their receptors, and subversion of their protective roles by bacterial pathogens

2016 ◽  
Vol 44 (6) ◽  
pp. 1651-1658 ◽  
Author(s):  
Jenny M. Woof
Keyword(s):  
Streptococcus Pyogenes ◽  
Immune Cells ◽  
Pathogenic Bacteria ◽  
Binding Proteins ◽  
Structural Basis ◽  
Immune Defence ◽  
Group B Streptococci ◽  
Interaction Partners ◽  
Group B ◽  
Recognition Capability

Immunoglobulins (Igs) play critical roles in immune defence against infectious disease. They elicit potent elimination processes such as triggering complement activation and engaging specific Fc receptors present on immune cells, resulting in phagocytosis and other killing mechanisms. Many important pathogens have evolved mechanisms to subvert or evade Ig-mediated defence. One such mechanism used by several pathogenic bacteria features proteins that bind the Ig Fc region and compromise engagement of host effector molecules. Examples include different IgA-binding proteins produced by Staphylococcus aureus, Streptococcus pyogenes, and group B streptococci, all of which interact with the same interdomain region on IgA Fc. Since this region also forms the interaction site for the major human IgA-specific Fc receptor CD89, the bacteria are able to evade CD89-mediated clearance mechanisms. Similar disruption of Ig effector function by pathogen Ig-binding proteins is evident in other species. Remarkably, all the Ig-binding proteins studied in detail to date are seen to target the CH2–CH3 domain interface in the Ig Fc region, suggesting a common mode of immune evasion. A second Ig subversion mechanism that has evolved independently in numerous pathogens involves proteases that cleave Ig molecules within their hinge regions, uncoupling the antigen recognition capability of the Fab region from clearance mechanisms elicited by the Fc region. The emerging understanding of the structural basis for the recognition of Igs as substrates for these proteases and as interaction partners for Ig-binding proteins may open up new avenues for treatment or vaccination.

scholarly journals Bacterial protein domains with a novel Ig-like fold target human CEACAM receptors

2020 ◽  
Author(s):  
Nina M. van Sorge ◽  
Daniel A. Bonsor ◽  
Liwen Deng ◽  
Erik Lindahl ◽  
Verena Schmitt ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Streptococcus Agalactiae ◽  
Neonatal Sepsis ◽  
Bacterial Protein ◽  
Human Pathogens ◽  
Critical Step ◽  
Mucosal Surfaces ◽  
Β Protein ◽  
Group B ◽  
Receptor Targets

AbstractStreptococcus agalactiae, also known as group B Streptococcus (GBS), is the major cause of neonatal sepsis in humans. A critical step to infection is adhesion of bacteria at mucosal surfaces. Though several GBS adhesins have been identified, the host receptor targets of these adhesins remain unknown. We report here that surface-expressed β protein from GBS binds to human CEACAM1 and CEACAM5 receptors. A crystal structure of the complex showed that the IgSF domain in β represents a novel Ig-fold subtype called IgI3, in which unique features allow binding to CEACAM1. Bioinformatic assessments revealed that this newly identified IgI3 fold is not exclusively present in GBS. Instead, the IgI3 fold is predicted to be present in adhesins from other clinically important human pathogens. We confirmed the interaction between CEACAM1 and the predicted IgI3-containing adhesin in two different streptococcal pathogens. Overall, our results indicate that the IgI3 fold could provide a broadly applied mechanism for bacteria to target CEACAMs.

scholarly journals Molecular Epidemiology and Distribution of Serotypes, Surface Proteins, and Antibiotic Resistance among Group B Streptococci in Italy

2007 ◽  
Vol 45 (9) ◽  
pp. 2909-2916 ◽  
Author(s):  
G. Gherardi ◽  
M. Imperi ◽  
L. Baldassarri ◽  
M. Pataracchia ◽  
G. Alfarone ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Molecular Epidemiology ◽  
Surface Proteins ◽  
Group B Streptococci ◽  
Group B

scholarly journals Human Milk Oligosaccharides Exhibit Biofilm Eradication Activity Against Matured Biofilms Formed by Different Pathogen Species

2022 ◽  
Vol 12 ◽  
Author(s):  
Sylwia Jarzynka ◽  
Riccardo Spott ◽  
Tinatini Tchatchiashvili ◽  
Nico Ueberschaar ◽  
Mark Grevsen Martinet ◽  
...  
Keyword(s):  
Human Milk ◽  
Pathogenic Bacteria ◽  
Biological Significance ◽  
Burkholderia Cenocepacia ◽  
Respiratory Pathogens ◽  
Human Milk Oligosaccharides ◽  
Group B Streptococci ◽  
Milk Oligosaccharides ◽  
Gram Positive ◽  
Group B

Human milk oligosaccharides (HMOs) have been shown to exhibit plenty of benefits for infants, such as prebiotic activity shaping the gut microbiota and immunomodulatory and anti-inflammatory activity. For some pathogenic bacteria, antimicrobial activity has been proved, but most studies focus on group B streptococci. In the present study, we investigated the antimicrobial and antibiofilm activities of the total and fractionated HMOs from pooled human milk against four common human pathogenic Gram-negative species (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Burkholderia cenocepacia) and three Gram-positive species (Staphylococcus aureus, Enterococcus faecium, and Enterococcus faecalis). The activity of HMOs against enterococci and B. cenocepacia are addressed here for the first time. We showed that HMOs exhibit a predominant activity against the Gram-positive species, with E. faecalis being the most sensitive to the HMOs, both in planktonic bacteria and in biofilms. In further tests, we could exclude fucosyllactose as the antibacterial component. The biological significance of these findings may lie in the prevention of skin infections of the mother’s breast as a consequence of breastfeeding-induced skin laceration and/or protection of the infants’ nasopharynx and lung from respiratory pathogens such as staphylococci.

scholarly journals Identification of Group B Streptococcal Sip Protein, Which Elicits Cross-Protective Immunity

2000 ◽  
Vol 68 (10) ◽  
pp. 5610-5618 ◽  
Author(s):  
Bernard R. Brodeur ◽  
Martine Boyer ◽  
Isabelle Charlebois ◽  
Josée Hamel ◽  
France Couture ◽  
...  
Keyword(s):  
Amino Acid ◽  
Molecular Mass ◽  
Protective Immunity ◽  
Genomic Library ◽  
Protein Band ◽  
Surface Proteins ◽  
Group B Streptococci ◽  
Universal Vaccine ◽  
Reading Frame ◽  
Group B

ABSTRACT A protein of group B streptococci (GBS), named Sip for surface immunogenic protein, which is distinct from previously described surface proteins, was identified after immunological screening of a genomic library. Immunoblots using a Sip-specific monoclonal antibody indicated that a protein band with an approximate molecular mass of 53 kDa which did not vary in size was present in every GBS strain tested. Representatives of all nine GBS serotypes were included in the panel of strains. Cloning and sequencing of the sip gene revealed an open reading frame of 1,305 nucleotides coding for a polypeptide of 434 amino acid residues, with a calculated pI of 6.84 and molecular mass of 45.5 kDa. Comparison of the nucleotide sequences from six different strains confirmed with 98% identity that the sip gene is highly conserved among GBS isolates. N-terminal amino acid sequencing also indicated the presence of a 25-amino-acid signal peptide which is cleaved in the mature protein. More importantly, immunization with the recombinant Sip protein efficiently protected CD-1 mice against deadly challenges with six GBS strains of serotypes Ia/c, Ib, II/R, III, V, and VI. The data presented in this study suggest that this highly conserved protein induces cross-protective immunity against GBS infections and emphasize its potential as a universal vaccine candidate.

scholarly journals Cross‐Protection between Group A and Group B Streptococci Due to Cross‐Reacting Surface Proteins

2000 ◽  
Vol 182 (1) ◽  
pp. 142-149 ◽  
Author(s):  
Margaretha Stålhammar‐Carlemalm ◽  
Thomas Areschoug ◽  
Charlotte Larsson ◽  
Gunnar Lindahl
Keyword(s):  
Cross Protection ◽  
Surface Proteins ◽  
Group B Streptococci ◽  
Group A ◽  
Group B
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