1. Uptake of Sialic Acid by Nontypeable Haemophilus influenzae Increases Complement Resistance through Decreasing IgM-Dependent Complement Activation
- Author
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Thomas J. Boltje, Sam J. Moons, Jeroen D. Langereis, Marien I. de Jonge, Marjolein M. P. Oerlemans, and Jurriaan J. A. Heming
- Subjects
Haemophilus Infections ,medicine.drug_class ,Immunology ,Antibiotics ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Synthetic Organic Chemistry ,Biology ,medicine.disease_cause ,Microbiology ,Haemophilus influenzae ,chemistry.chemical_compound ,Classical complement pathway ,All institutes and research themes of the Radboud University Medical Center ,medicine ,Humans ,Complement Activation ,Respiratory tract infections ,Biological Transport ,Complement System Proteins ,biology.organism_classification ,Molecular Pathogenesis ,Antibodies, Bacterial ,N-Acetylneuraminic Acid ,Sialic acid ,Complement system ,Infectious Diseases ,Mechanism of action ,chemistry ,Immunoglobulin M ,Parasitology ,medicine.symptom ,Bacteria - Abstract
Although nontypeable Haemophilus influenzae (NTHi) is a human-specific nasopharyngeal commensal bacterium, it also causes upper respiratory tract infections in children and lower respiratory tract infections in the elderly, resulting in frequent antibiotic use. The transition from symbiotic colonizing bacterium to opportunistic pathogen is not completely understood. Incorporation of sialic acids into lipooligosaccharides is thought to play an important role in bacterial virulence. It has been known for more than 25 years that sialic acids increase resistance to complement-mediated killing; however, the mechanism of action has not been elucidated thus far. Here, we provide evidence that growth of NTHi in the presence of sialic acids Neu5Ac and Neu5Gc decreases complement-mediated killing through abrogating the classical pathway of complement activation by preventing mainly IgM antibody binding to the bacterial surface. Therefore, strategies that interfere with uptake or incorporation of sialic acids into the lipooligosaccharide, such as novel antibiotics and vaccines, might be worth exploring to prevent or treat NTHi infections.
- Published
- 2019
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