Delineation of B-cell Epitopes of Salmonella enterica serovar Typhi Hemolysin E: Potential antibody therapeutic target
Abstract Hemolysin E (HlyE) is an immunogenic novel pore-forming toxin involved in the pathogenesis of typhoid fever. Thus, mapping of B-cell epitopes of Salmonella enterica serovar Typhi (S. Typhi) is critical to identify key immunogenic regions of HlyE. A random 20-mer peptide library was used for...
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2017-05-01
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doaj-a4d6c9f4fd8d4388a6dd540c4d1fa61a2020-12-08T01:08:04ZengNature Publishing GroupScientific Reports2045-23222017-05-017111410.1038/s41598-017-01987-8Delineation of B-cell Epitopes of Salmonella enterica serovar Typhi Hemolysin E: Potential antibody therapeutic targetChai Fung Chin0Jing Yi Lai1Yee Siew Choong2Amy Amilda Anthony3Asma Ismail4Theam Soon Lim5Institute for Research in Molecular Medicine, Universiti Sains MalaysiaInstitute for Research in Molecular Medicine, Universiti Sains MalaysiaInstitute for Research in Molecular Medicine, Universiti Sains MalaysiaInstitute for Research in Molecular Medicine, Health Campus, Universiti Sains MalaysiaInstitute for Research in Molecular Medicine, Health Campus, Universiti Sains MalaysiaInstitute for Research in Molecular Medicine, Universiti Sains MalaysiaAbstract Hemolysin E (HlyE) is an immunogenic novel pore-forming toxin involved in the pathogenesis of typhoid fever. Thus, mapping of B-cell epitopes of Salmonella enterica serovar Typhi (S. Typhi) is critical to identify key immunogenic regions of HlyE. A random 20-mer peptide library was used for biopanning with enriched anti-HlyE polyclonal antibodies from typhoid patient sera. Bioinformatic tools were used to refine, analyze and map the enriched peptide sequences against the protein to identify the epitopes. The analysis identified both linear and conformational epitopes on the HlyE protein. The predicted linear GAAAGIVAG and conformational epitope PYSQESVLSADSQNQK were further validated against the pooled sera. The identified epitopes were then used to isolate epitope specific monoclonal antibodies by antibody phage display. Monoclonal scFv antibodies were enriched for both linear and conformational epitopes. Molecular docking was performed to elucidate the antigen-antibody interaction of the monoclonal antibodies against the epitopes on the HlyE monomer and oligomer structure. An in-depth view of the mechanistic and positional characteristics of the antibodies and epitope for HlyE was successfully accomplished by a combination of phage display and bioinformatic analysis. The predicted function and structure of the antibodies highlights the possibility of utilizing the antibodies as neutralizing agents for typhoid fever.https://doi.org/10.1038/s41598-017-01987-8 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chai Fung Chin Jing Yi Lai Yee Siew Choong Amy Amilda Anthony Asma Ismail Theam Soon Lim |
spellingShingle |
Chai Fung Chin Jing Yi Lai Yee Siew Choong Amy Amilda Anthony Asma Ismail Theam Soon Lim Delineation of B-cell Epitopes of Salmonella enterica serovar Typhi Hemolysin E: Potential antibody therapeutic target Scientific Reports |
author_facet |
Chai Fung Chin Jing Yi Lai Yee Siew Choong Amy Amilda Anthony Asma Ismail Theam Soon Lim |
author_sort |
Chai Fung Chin |
title |
Delineation of B-cell Epitopes of Salmonella enterica serovar Typhi Hemolysin E: Potential antibody therapeutic target |
title_short |
Delineation of B-cell Epitopes of Salmonella enterica serovar Typhi Hemolysin E: Potential antibody therapeutic target |
title_full |
Delineation of B-cell Epitopes of Salmonella enterica serovar Typhi Hemolysin E: Potential antibody therapeutic target |
title_fullStr |
Delineation of B-cell Epitopes of Salmonella enterica serovar Typhi Hemolysin E: Potential antibody therapeutic target |
title_full_unstemmed |
Delineation of B-cell Epitopes of Salmonella enterica serovar Typhi Hemolysin E: Potential antibody therapeutic target |
title_sort |
delineation of b-cell epitopes of salmonella enterica serovar typhi hemolysin e: potential antibody therapeutic target |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-05-01 |
description |
Abstract Hemolysin E (HlyE) is an immunogenic novel pore-forming toxin involved in the pathogenesis of typhoid fever. Thus, mapping of B-cell epitopes of Salmonella enterica serovar Typhi (S. Typhi) is critical to identify key immunogenic regions of HlyE. A random 20-mer peptide library was used for biopanning with enriched anti-HlyE polyclonal antibodies from typhoid patient sera. Bioinformatic tools were used to refine, analyze and map the enriched peptide sequences against the protein to identify the epitopes. The analysis identified both linear and conformational epitopes on the HlyE protein. The predicted linear GAAAGIVAG and conformational epitope PYSQESVLSADSQNQK were further validated against the pooled sera. The identified epitopes were then used to isolate epitope specific monoclonal antibodies by antibody phage display. Monoclonal scFv antibodies were enriched for both linear and conformational epitopes. Molecular docking was performed to elucidate the antigen-antibody interaction of the monoclonal antibodies against the epitopes on the HlyE monomer and oligomer structure. An in-depth view of the mechanistic and positional characteristics of the antibodies and epitope for HlyE was successfully accomplished by a combination of phage display and bioinformatic analysis. The predicted function and structure of the antibodies highlights the possibility of utilizing the antibodies as neutralizing agents for typhoid fever. |
url |
https://doi.org/10.1038/s41598-017-01987-8 |
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