Delineation of B-cell Epitopes of Salmonella enterica serovar Typhi Hemolysin E: Potential antibody therapeutic target

Scientific Reports
Chai Fung ChinTheam Soon Lim

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...Continue Reading

References

Oct 5, 1990·Journal of Molecular Biology·S F AltschulD J Lipman
Dec 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·T M FieserR A Lerner
Jul 1, 1994·Trends in Biotechnology·R CorteseA Nicosia
Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
Feb 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·B ForoodK P Nambiar
Jan 1, 1996·Annual Review of Immunology·B D Jones, S Falkow
Jan 1, 1996·Advances in Protein Chemistry·M Sela, I Pecht
Sep 28, 2000·The Journal of Biological Chemistry·A AtkinsJ Green
Jun 5, 2003·Proteins·Rong ChenZhiping Weng
Feb 8, 2006·Trends in Microbiology·Lisa M MullenBrian Henderson
Nov 1, 2006·Protein Science : a Publication of the Protein Society·Min-Yi Shen, Andrej Sali
Dec 8, 2006·Nucleic Acids Research·Itay MayroseTal Pupko
Nov 6, 2007·Bioinformatics·Itay MayroseTal Pupko
Aug 22, 2008·International Journal of Medical Microbiology : IJMM·Christine von RheinAlbrecht Ludwig
Dec 6, 2008·BMC Bioinformatics·Julia PonomarenkoBjoern Peters
Apr 21, 2009·Methods in Molecular Biology·Marc H V Van Regenmortel
Mar 27, 2010·Journal of Biomedicine & Biotechnology·Jian HuangFeng-Biao Guo
Apr 1, 2010·BMC Bioinformatics·Hifzur R Ansari, Gajendra P S Raghava
May 5, 2010·Nucleic Acids Research·Mickael GoujonRodrigo Lopez
Aug 7, 2010·Advances in Experimental Medicine and Biology·Stuart HuntPeter J Artymiuk
Oct 22, 2010·Immunome Research·Hifzur Rahman Ansari, Gajendra Ps Raghava
Apr 28, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Guillaume CastelNoël Tordo
Sep 10, 2014·Current Protocols in Bioinformatics·Benjamin Webb, Andrej Sali
Apr 20, 2016·Toxicon : Official Journal of the International Society on Toxinology·Bee Nar LimTheam Soon Lim

❮ Previous
Next ❯

Methods Mentioned

BETA
electron microscopy
phage display
ELISA
ELISAs
electrophoresis
pull down
pulldown
X-ray
pull-down

Software Mentioned

Clustal Omega
BCPREDS
Basic Local Alignment Search Tool ( BLAST )
PROCHECK
PepSurf
EpiSearch
ElliPro
MODELLER
CBTOPE
Pepitope

Related Concepts

Related Feeds

Bacteriophage: Phage Therapy

Phage therapy uses bacterial viruses (bacteriophages) to treat bacterial infections and is widely being recognized as an alternative to antibiotics. Here is the latest research.