A5002914719- Streptococcal Infections and Treatments
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Neonatal and Maternal Infections
- Antimicrobial Resistance in Staphylococcus
- Galectins and Cancer Biology
- Antimicrobial Peptides and Activities
- Immunodeficiency and Autoimmune Disorders
- Bacteriophages and microbial interactions
- Computational Drug Discovery Methods
- Orthopedic Infections and Treatments
- Advanced Biosensing Techniques and Applications
- Immune Response and Inflammation
- Blood groups and transfusion
- Infections and bacterial resistance
- Bacterial Identification and Susceptibility Testing
- Toxin Mechanisms and Immunotoxins
- Autoimmune Bullous Skin Diseases
- T-cell and B-cell Immunology
- Enzyme Production and Characterization
- Diabetes and associated disorders
- Biochemical and Structural Characterization
- Platelet Disorders and Treatments
- Orthopaedic implants and arthroplasty
- Pneumonia and Respiratory Infections
Lund University
2016-2025
National Postdoctoral Association
2022
Biology of Infection
2001-2017
Skåne University Hospital
2012
Rockefeller University
2003-2010
Staphylococcus aureus is the causative agent of several serious infectious diseases. The emergence antibiotic-resistant S. strains has resulted in significant treatment difficulties, intensifying need for new antimicrobial agents. Toward this end, we have developed a novel chimeric bacteriophage (phage) lysin that active against staphylococci, including methicillin-resistant (MRSA). (called ClyS) was obtained by fusing N-terminal catalytic domain Twort phage with C-terminal cell...
ABSTRACT Streptococcus pyogenes secretes a specific immunoglobulin G (IgG)-protease, SpeB, as well the IgG glycan-hydrolyzing enzyme EndoS. Here we show that SpeB also degrades IgA, IgM, IgD, and IgE. We EndoS only hydrolyzes glycan moiety on native but not denatured IgG. Thus, has broad immunoglobulin-degrading activity, while is highly for
Previous work has indicated a crucial role for the extracellular cysteine proteinase of Streptococcus pyogenes in pathogenicity and virulence this important human pathogen. Here we find that purified streptococcal releases biologically active kinins from their precursor protein, H-kininogen, vitro, kininogens present plasma, ex vivo. Kinin liberation plasma is due to direct action on kininogens, does not involve previous activation prekallikrein, physiological kininogenase. Judged amount...
IgG antibodies are potent inducers of proinflammatory responses. During autoimmune diseases such as arthritis and systemic lupus erythematosus, autoantibodies responsible for the chronic inflammation destruction healthy tissues by cross-linking Fc receptors on innate immune effector cells. The sugar moiety attached to asparagine-297 residue in constant domain antibody is critical overall structure function molecule. Removal this leads loss activity, suggesting that vivo modulation...
Many bacteria have evolved ways to interact with glycosylation functions of the immune system their hosts. Streptococcus pyogenes [GAS (group A Streptococcus)] secretes enzyme EndoS that cleaves glycans on human IgG and impairs effector antibody. The ndoS gene, encoding EndoS, has, until now, been thought be conserved throughout serotypes. However, in present study, we identify EndoS2, an endoglycosidase serotype M49 GAS strains. We characterized EndoS2 corresponding ndoS2 gene using...
Rheumatoid arthritis-associated joint pain is frequently observed independent of disease activity, suggesting unidentified mechanisms. We demonstrate that antibodies binding to cartilage, specific for collagen type II (CII) or cartilage oligomeric matrix protein (COMP), elicit mechanical hypersensitivity in mice, uncoupled from visual, histological and molecular indications inflammation. Cartilage antibody-induced pain-like behavior does not depend on complement activation inflammation, but...
EndoS from Streptococcus pyogenes efficiently hydrolyzes the functionally important and conserved N-linked glycan of IgG in human blood. Repeated i.v. administration rabbits completely glycans whole pool, despite generation anti-EndoS antibodies. had no apparent effects on health animals. hydrolysis has profound effector functions, such as complement activation Fc receptor binding, suggesting that enzyme could be used an immunomodulatory therapeutic agent against IgG-mediated diseases. We...
The glycosylation status of IgG has been implicated in the pathology rheumatoid arthritis. Earlier, we reported identification a novel secreted endo-beta-N-acetylglucosaminidase (EndoS), by Streptococcus pyogenes that specifically hydrolyzes beta-1,4-di-N-acetylchitobiose core asparagine-linked glycan human IgG. Here, analyzed arthritogenicity EndoS-treated collagen type II (CII)-specific mouse mAb vivo. Endoglycosidase treatment antibodies inhibited induction arthritis (BALB/c x B10.Q) F1...
BackgroundThe human pathogen Streptococcus pyogenes produces an endoglycosidase, EndoS that hydrolyzes the chitobiose core of asparagine-linked glycan on heavy chain IgG. IgG-binding to Fc gamma receptors (FcγR) leukocytes triggers effector functions including phagocytosis, oxidative burst and release inflammatory mediators. The interactions between FcγR domain IgG depend glycosylation state.Methodology/Principal FindingsHere we show for first time all four subclasses (IgG1-4), in purified...
Background. Anti-glomerular basement membrane (anti-GBM) disease often results in end-stage renal failure despite therapy with plasma exchange and immunosuppressive drugs. The newly discovered streptococcal enzymes IgG-degrading enzyme of S.pyogenes (IdeS) endoglycosidase S (EndoS) act remarkable specificity on circulating IgG. In this study, we investigate their ability vivo to prevent damage mediated by kidney-bound antibodies a mouse model anti-GBM disease. Methods. Anti-GBM was induced...
Anti-neutrophil cytoplasmic autoantibodies (ANCA) directed against myeloperoxidase (MPO) and proteinase 3 (Pr3) are considered pathogenic in ANCA-associated necrotizing crescentic glomerulonephritis (NCGN) vasculitis. Modulation of ANCA IgG glycosylation may potentially reduce its pathogenicity by abolishing Fc receptor–mediated activation leukocytes complement. Here, we investigated whether hydrolysis the bacterial enzyme endoglycosidase S (EndoS) attenuates ANCA-mediated NCGN. In vitro,...
Immunoglobulin G (IgG) glycosylation modulates antibody activity and represents a major source of heterogeneity within preparations. Depending on their pattern, individual IgG glycovariants present in recombinant preparations may trigger effects ranging from enhanced pro-inflammatory to increased anti-inflammatory activity. In contrast, reduction beyond the central mannose core is generally believed result impaired However, this study reveals that mono- or disaccharide structure consisting...
Enzymes that affect glycoproteins of the human immune system, and thereby modulate defense responses, are abundant among bacterial pathogens. Two endoglycosidases from pathogen Streptococcus pyogenes, EndoS EndoS2, have recently been shown to hydrolyze N-linked glycans immunoglobulin G. However, detailed characterization comparison hydrolyzing activities not performed. In present study, we set out characterize enzymes by comparing EndoS2 on a selection therapeutic monoclonal antibodies...
BackgroundEffector functions of IgG Abs are regulated by their Fc N-glycosylation pattern. glycans that lack galactose and terminal sialic acid residues correlate with the severity inflammatory (auto)immune disorders have also been linked to protection against viral infection discussed in context vaccine-induced protection. In contrast, sialylated shown immunosuppressive effects.ObjectiveWe sought investigate glycosylation programming during germinal center (GC) reaction following...
The human pathogen Streptococcus pyogenes primarily infects the upper respiratory tract and skin, but occasionally it disseminates causes severe invasive disease with high mortality. This study revealed that activity of extracellular EndoS, which hydrolyzes functionally important N-linked oligosaccharides on opsonizing immunoglobulin G (IgG), contributes to increased survival S. in blood ex vivo. inability kill bacteria is due reduced binding IgG Fc receptors impaired classical...
Granulocyte chemotactic protein 2 (GCP-2)/CXCL6 is a CXC chemokine expressed by macrophages and epithelial mesenchymal cells during inflammation. Through binding activation of its receptors (CXCR1 CXCR2), it exerts neutrophil-activating angiogenic activities. Here we show that GCP-2/CXCL6 itself antibacterial. Antibacterial activity against gram-positive gram-negative pathogenic bacteria relevance to mucosal infections was seen at submicromolar concentrations (minimal bactericidal...
Bacterial engagement of specific host tissue structures can be a means targeting pathogen to particular niche, establishing persistent infections and inducing invasion. In this context, primary adhesion is often the first crucial colonization step allowing pathogens withstand mechanical clearing mechanisms host. As consequence, bacteria have evolved adhesins with capacity mediate interaction between microorganism Here we describe collagen VI as novel target for adherence Streptococcus...