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Nontypeable haemophilus influenzae P5 binds human C4b-binding protein, promoting serum resistance

Authors :
Thofte, Oskar
Bettoni, Serena
Su, Yu-Ching
Thegerström, John
Jonsson, Sandra
Mattsson, Emma
Sandblad, Linda
Martí, Sara
Garmendia, Junkal
Blom, Anna M.
Riesbeck, Kristian
Swedish Heart-Lung Foundation
Swedish Research Council
Anna och Edwin Bergers Stiftelse
Torsten Söderberg Foundation
Royal Physiographic Society of Lund
Lund University
O. E. och Edla Johanssons Foundation
Stiftelsen Längmanska kulturfonden
Tore Nilsson’s Foundation
Skåne Regional Council
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.

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.).

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