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 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.

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 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.

Use of Fc-binding proteins to identify cell surface and secreted antigens associated with group B streptococci

1990 ◽  
pp. 161-179
Author(s):  
L. Jeannine Brady ◽  
Corey Musselman ◽  
Colleen Chun ◽  
Elia M. Ayoub ◽  
Michael D.P. Boyle
Keyword(s):  
Cell Surface ◽  
Binding Proteins ◽  
Group B Streptococci ◽  
Group B ◽  
Secreted Antigens

High resolution spot scan imaging of frozen, hydrated actin bundles with 400kV electrons

1992 ◽  
Vol 50 (1) ◽  
pp. 512-513
Author(s):  
J. Jakana ◽  
M.F. Schmid ◽  
P. Matsudaira ◽  
W. Chiu
Keyword(s):  
High Resolution ◽  
Binding Proteins ◽  
Actin Binding ◽  
Eukaryotic Cells ◽  
Dimensional Structure ◽  
Structural Basis ◽  
Actin Bundle ◽  
Actin Bundles ◽  
3 Dimensional ◽  
Macromolecular Assembly

Actin is a protein found in all eukaryotic cells. In its polymerized form, the cells use it for motility, cytokinesis and for cytoskeletal support. An example of this latter class is the actin bundle in the acrosomal process from the Limulus sperm. The different functions actin performs seem to arise from its interaction with the actin binding proteins. A 3-dimensional structure of this macromolecular assembly is essential to provide a structural basis for understanding this interaction in relationship to its development and functions.

Susceptibility to Six Antibiotics of Group B Streptococci Isolated from Cerebrospinal Fluid

1985 ◽  
Vol 17 (2) ◽  
pp. 191-193
Author(s):  
Chris Mulder ◽  
Pieter Bol ◽  
Arjan Nabbe ◽  
Bob Zanen
Keyword(s):  
Cerebrospinal Fluid ◽  
Group B Streptococci ◽  
Group B

scholarly journals Influence of group B streptococci on piglet pulmonary artery response to bradykinin

1999 ◽  
Vol 86 (1) ◽  
pp. 61-65 ◽  
Author(s):  
Richard M. Whitehurst ◽  
Rachel Laskey ◽  
Ronald N. Goldberg ◽  
Donald Herbert ◽  
Cornelius Van Breemen
Keyword(s):  
Pulmonary Artery ◽  
Contractile Response ◽  
Isometric Force ◽  
Control Group ◽  
Relaxed Controls ◽  
Vascular Response ◽  
Group B Streptococci ◽  
Resting Tension ◽  
Neonatal Group ◽  
Group B

To study whether a sepsis-induced increase in des-Arg9-bradykinin (des-Arg9-BK) and bradykinin (BK) B1-receptor activity participates in the observed increase in pulmonary vascular resistance in neonatal group B streptococcal sepsis (GBS), isometric force bioassays of pulmonary artery (PA) rings were studied, after 4-h exposure to either Krebs or GBS, by using the following protocols: 1) BK dose-response curve, 2) vascular response to BK with N G-nitro-l-arginine methyl ester (l-NAME), and 3) response to des-Arg9-BK (BK metabolite and B1 agonist). PA rings exposed to BK resulted in contraction in the GBS group and a decrease in resting tension in the Control group ( P = 0.034) at a concentration of 10−5 M. GBS-treated PA rings contracted more to des-Arg9-BK than did Controls ( P < 0.001). BK (10−6 M) relaxed preconstricted PA rings incubated in GBS less than BK relaxed Controls ( P < 0.001), and preincubation withl-NAME decreased relaxation in both. These results suggest that GBS decreased endothelium-dependent BK relaxation and increased contractile response to des-Arg9-BK. We speculate that this occurs secondary to upregulation of B1 receptors reflected by B1-agonist-mediated PA contraction.

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