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Nontypeable haemophilus influenzae P5 binds human C4b-binding protein, promoting serum resistance
- Source :
- Dipòsit Digital de la UB, Universidad de Barcelona, The Journal of Immunology Author Choice, Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2021
- Publisher :
- Umeå universitet, Institutionen för molekylärbiologi (Medicinska fakulteten), 2021.
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Abstract
- Nontypeable Haemophilus influenzae (NTHi) is a Gram-negative human pathogen that causes infections mainly in the upper and lower respiratory tract. The bacterium is associated with bronchitis and exacerbations in patients suffering from chronic obstructive pulmonary disease and frequently causes acute otitis media in preschool children. We have previously demonstrated that the binding of C4b binding protein (C4BP) is important for NTHi complement evasion. In this study, we identified outer membrane protein 5 (P5) of NTHi as a novel ligand of C4BP. Importantly, we observed significantly lower C4BP binding and decreased serum resistance in P5-deficient NTHi mutants. Surface expression of recombinant P5 on Escherichia coli conferred C4BP binding and consequently increased serum resistance. Moreover, P5 expression was positively correlated with C4BP binding in a series of clinical isolates. We revealed higher levels of P5 surface expression and consequently more C4BP binding in isolates from the lower respiratory tract of chronic obstructive pulmonary disease patients and tonsil specimens compared with isolates from the upper respiratory tract and the bloodstream (invasive strains). Our results highlight P5 as an important protein for protecting NTHi against complement-mediated killing.<br />This work was supported by the Swedish Heart Lung Foundation (20180401), the Swedish Research Council (2019-01053 to K.R.; 2018-02392 to A.M.B.), the Anna och Edwin Berger foundation (to K.R.), the Torsten Söderberg Foundation (to A.M.B.), the Royal Physiographical Society in Lund Hedda and John Forssman Foundation (to O.T. and S.B.), the O. E. och Edla Johanssons Foundation (to S.B.), the Längmanska Kulturfonden (to S.B.), the Tore Nilsson’s Foundation (to S.B.), and Skåne County Council’s Research and Development Foundation (to K.R. and A.M.B.).
- Subjects :
- Male
Infectious Disease and Host Response
Haemophilus Infections
Bacteremia
Ligands
Pulmonary Disease, Chronic Obstructive
Escherichia coli
otorhinolaryngologic diseases
Humans
Child
Aged
Aged, 80 and over
Organisms, Genetically Modified
Complement C4b-Binding Protein
Proteins
Immunology in the medical area
Bacils
Complement System Proteins
Middle Aged
Haemophilus influenzae
Recombinant Proteins
Bacillus (Bacteria)
Tonsillitis
Pathogenic bacteria
Immunologi inom det medicinska området
Bacteris patògens
Female
Proteïnes
Bacterial Outer Membrane Proteins
Protein Binding
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Dipòsit Digital de la UB, Universidad de Barcelona, The Journal of Immunology Author Choice, Digital.CSIC. Repositorio Institucional del CSIC, instname
- Accession number :
- edsair.pmid.dedup....ac763e49333409d836e0d94221664a1e