University of Leicester
Browse

Streptococcus pneumoniae Cell Wall-Localized Trigger Factor Elicits a Protective Immune Response and Contributes to Bacterial Adhesion to the Host.

Download (1.49 MB)
journal contribution
posted on 2019-06-11, 15:06 authored by A Cohen, S Troib, S Dotan, H Najmuldeen, H Yesilkaya, T Kushnir, M Shagan, M Portnoi, H Nachmani, R Benisty, M Tal, R Ellis, V Chalifa-Caspi, R Dagan, YM Nebenzahl
Trigger factor (TF) has a known cytoplasmic function as a chaperone. In a previous study we showed that pneumococcal TF is also cell-wall localized and this finding combined with the immunogenic characteristic of TF, has led us to determine the vaccine potential of TF and decipher its involvement in pneumococcal pathogenesis. Bioinformatic analysis revealed that TF is conserved among pneumococci and has no human homologue. Immunization of mice with recombinant (r)TF elicited a protective immune response against a pneumococcal challenge, suggesting that TF contributes to pneumococcal pathogenesis. Indeed, rTF and an anti-rTF antiserum inhibited bacterial adhesion to human lung derived epithelial cells, indicating that TF contributes to the bacterial adhesion to the host. Moreover, bacteria lacking TF demonstrated reduced adhesion, in vitro, to lung-derived epithelial cells, neural cells and glial cells. The reduced adhesion could be restored by chromosomal complementation. Furthermore, bacteria lacking TF demonstrated significantly reduced virulence in a mouse model. Taken together, the ability of rTF to elicit a protective immune response, involvement of TF in bacterial adhesion, conservation of the protein among pneumococcal strains and the lack of human homologue, all suggest that rTF can be considered as a future candidate vaccine with a much broader coverage as compared to the currently available pneumococcal vaccines.

Funding

This work was supported by grants from the Israeli Ministry of Health numbers 4776 and 5540, 3000003867, from the Center of Emerging Diseases #2506, from the Israel Academy of Science 613/04, The Israel Ministry of Commerce and Industry to NasVax Ltd., European Community 7th FP: CAREPNEUMO 223111, from BGNegev Biotechnology to YMN.

History

Citation

Scientific Reports, 2019, 9, Article number: 4295

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Infection, Immunity and Inflammation

Version

  • VoR (Version of Record)

Published in

Scientific Reports

Publisher

Nature Research (part of Springer Nature)

eissn

2045-2322

Acceptance date

2018-10-24

Copyright date

2019

Available date

2019-06-11

Publisher version

https://www.nature.com/articles/s41598-019-40779-0

Notes

Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-019-40779-0.

Language

en

Usage metrics

    University of Leicester Publications

    Categories

    No categories selected

    Keywords

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC