Extracellular DNA within a Nontypeable Haemophilus influenzae-Induced Biofilm Binds Human Beta Defensin-3 and Reduces Its Antimicrobial Activity
| Autor: | Glen McGillivary, Lauren O. Bakaletz, Eric A. Jones |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
DNA
Bacterial Male Haemophilus Infections beta-Defensins Biology medicine.disease_cause Article Microbiology Haemophilus influenzae law.invention Chinchilla law otorhinolaryngologic diseases medicine Animals Deoxyribonuclease I Humans Immunology and Allergy Immunosuppression Therapy Innate immune system Effector Infant Newborn Biofilm Infant Biofilm matrix biochemical phenomena metabolism and nutrition Immunity Innate Recombinant Proteins In vitro Otitis Media Beta defensin Biofilms Child Preschool Recombinant DNA Female Protein Binding |
| Zdroj: | Journal of Innate Immunity. 5:24-38 |
| ISSN: | 1662-8128 1662-811X |
| Popis: | Biofilms formed by nontypeable Haemophilus influenzae (NTHI) are associated with multiple chronic infections of the airway, including otitis media. Extracellular DNA (eDNA) is part of the biofilm matrix and serves as a structural component. Human β-defensin-3 (hBD-3) is a cationic antimicrobial host defense protein (AMP) critical to the protection of the middle ear. We hypothesized that anionic eDNA could interact with and bind hBD-3 and thus shield NTHI in biofilms from its antimicrobial activity. We demonstrated that recombinant hBD-3 [(r)hBD-3] bound eDNA in vitro and that eDNA in biofilms produced by NTHI in the chinchilla middle ear co-localized with the orthologue of this AMP. Incubation of physiological concentrations of (r)hBD-3 with NTHI genomic DNA abrogated the ability of this innate immune effector to prevent NTHI from forming robust biofilms in vitro. Establishment of NTHI biofilms in the presence of both DNase I and (r)hBD-3 resulted in a marked reduction in the overall height and thickness of the biofilms and rescued the antimicrobial activity of the AMP. Our results demonstrated that eDNA in NTHI biofilms sequestered hBD-3 and thus diminished the biological activity of an important effector of innate immunity. Our observations have important implications for chronicity of NTHI-induced diseases. |
| Databáze: | OpenAIRE |
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