Antigenic properties of Finegoldia magna protein L and Type IV Pilin PilA for in-silico multi epitope peptide vaccine designing
Subject Areas : Immunology
1 - Department of Genetics, Fars Academic Center for Education, Culture and Research, ACECR, Shiraz, Iran
Keywords: Finegoldia magna, protein L, type IV pilin PilA, multi epitope peptide vaccine, in-silico,
Abstract :
Background and Objectives: Finegoldia magna is a potential opportunistic pathogen for humans. F. magna as the most frequent pathogenic species of gram positive anaerobic cocci accounts for up to 5-12% of all anaerobic infections. F. magna possess Protein L super antigen and Type IV Pilin PilA as invaluable proteins for designing multi epitope peptide vaccines in current study.Materials and Methods: In this study, immunoinformatics tools were used to predict B and T cell epitopes of Protein L and Type IV Pilin PilA. The epitopes were evaluated for antigenicity, allergenicity and binding energy to appropriate HLA alleles and then were fused together by GPGPG and EAAAK spacers. Vibrio cholera Toxin B Subunit was introduced at N-terminus of the constructed vaccine as adjuvant, and with an eye on further identification and purification, a 6×HisTag was introduced at C-terminus. Codon optimization performed for further expression in Escherichia coli host. The amino acid sequence of the multi epitope peptide vaccine used for 3D structure prediction and refinement. Then structural evaluation via ramachandran plot analysis performed. Physicochemical properties and solubility of the constructed vaccine was also studied.Results: Results showed the selected epitopes with high antigenicity and no allergenicity. These epitopes manifest high affinity toward recommended HLA alleles. The predicted 3D model of constructed vaccine showed high stability, solubility and half-life for expression in E. coli host. Conclusion: In this study, Protein L and Type IV Pilin PilA used for in-silico designing an effective vaccine against F. magna. Further in-vitro/vivo studies are recommended.
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pathogens. FEMS Microbiol Rev 2013 37 (4): 520-553.
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from orthopedic joint implant-associated infections. J Clin Microbiol. 2017 55 (11):
3283-3291.
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magna in a non-puerperal woman. Anaerobe. 2017 47: 183-184.
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Microbiol. 2007 45 (9): 8 9– 8 8
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men of infertile couples: metagenomic sequencing reveals relationships of seminal microbiota
to semen quality. PLoS NE 2014 9 (10): e110152.
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Levinson1 A. The b cell super antigen Finegoldia magna protein L causes pulmonary
inflammation by a mechanism dependent on myd88 but not b cells or immunoglobulins.
Inflamm Res. 2012 61 (2): 6 – 69
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surface of Finegoldia magna - A Gram positive anaerobic cocci. Anaerobe 2014 27: 40-49.
10. Skwarczynski M, Totha I. Peptide-based synthetic vaccines. Chem Sci. 2016 7 (2): 842-854.
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antigens and subunit vaccines. BMC Bioinformatics 2007 5: 8-4.
12. Larsen J, Lund , Nielsen M. Improved method for predicting linear B cell epitopes.
Immunome Res. 2006 24: 2-2.
13. Saha S, Raghava G. AlgPred: prediction of allergenic proteins and mapping of IgE epitopes.
Nucleic Acids Res 2006 34: 202-209.
14. Vita R, arebski L, Greenbaum J, Emami H, Hoof I. The immune epitope database 2.0.
Nucleic Acids Res. 2009 38: 854-862.
15. Paul S, Arlehamn C, Scriba T, Dillon M, seroff C. Development and validation of a broad
scheme for prediction of HLA class II restricted T cell epitopes. J Immunol Methods. 2015
422: 28-34.
16. Alam N, Goldstein , ia B, Porter K, Kozakov D, Schueler-Furman . High-resolution
global peptide-protein docking using fragments-based PIPER-FlexPepDock. PLoS Comput.
Biol. 2017 13: e1005905.
17. Buchan D, Jones D. The PSIPRED protein analysis workbench: 20 years on. Nucleic Acids
Res. 2019 47: 402-407.
18. ang J, hang . I-TASSER server: new development for protein structure and function
predictions. Nucleic Acids Res. 2015 43: 174-181.
19. u D, hang . Improving the physical realism and structural accuracy of protein models by
a two-step atomic-level energy minimization. Biophys J. 2011 101: 2525-2534.
20. Lovell S, Davis I, Arendall B, Bakker P. Structure validation by Cα geometry: ϕ, ψ and Cβ
deviation. Proteins. 2003 50 (3): 7–
21. Gasteiger E, Hoogland C, Gattiker A, Duvaud S, Wilkins M. (2005). Protein identification
and analysis tools on the ExPASy server. I In: Walker J.M. (eds) The Proteomics Protocols
Handbook. Humana Press.
22. Hebditch M, Carballo-Amador MA, Charonis S, Curtis R, Warwicker J. Protein-Sol: a web
tool for predicting protein solubility from sequence. Bioinformatics 2017 33 (19): 3098-3100.
23. Puigbò P, Guzmán E, Romeu A, Garcia-Vallvé S. PTIMI ER: a web server for optimizing
the codon usage of DNA sequences. Nucleic Acids Res. 2007 35: 126-131.
24. Saha CK, Mahbub Hasan M, Hossain S, Jahan A, Azad AK. In silico identification and
characterization of common epitope-based peptide vaccine for Nipah and Hendra viruses.
Asian Pac J Trop Med 2017 10 (6): 529-538.
25. Jin , Sun T, ia , Wei , Song . ptimized expression, purification of herpes B virus GD
protein in Escherichia coli, and production of its monoclonal antibodies. Jundishapur J
Microbiol 2016 9 (3): e32183.
26. Saadi M, Karkhah A, Nouri HR. Development of a multi-epitope peptide vaccine inducing
robust T cell responses against brucellosis using immunoinformatics based approaches. Infect.
Genet. Evol. 2017 51: 227-234.
27. Stratmann T. Cholera toxin subunit B as adjuvant-an accelerator in protective immunity and a
break in autoimmunity. Vaccines 2015 3 (3): 579-596.
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due to Finegoldia magna. Case Rep Infect Dis. .793053 2014
2. Murphy EC, Frick IM. Gram-positive anaerobic cocci–commensals and opportunistic
pathogens. FEMS Microbiol Rev 2013 37 (4): 520-553.
3. Söderquist B, Björklund S, Hellmark B, Jensen A, Brüggemann H. Finegoldia magna isolated
from orthopedic joint implant-associated infections. J Clin Microbiol. 2017 55 (11):
3283-3291.
4. Cobo F, Rodríguez-Granger J, Sampedro A, Navarro-Marí JM. Breast abscess due to Finegoldia
magna in a non-puerperal woman. Anaerobe. 2017 47: 183-184.
5. Citron D, Goldstein E, Merriam C, Lipsky B, Abramson M. Bacteriology of
moderate-to-severe diabetic foot infections and in vitro activity of antimicrobial agents. J Clin
Microbiol. 2007 45 (9): 8 9– 8 8
6. Rosenthal ME, Rojtman AD, Frank E. Finegoldia magna (formerly e tostre tococcus
magnus): An overlooked etiology for toxic shock syndrome? Med. Hypotheses 2012 79 (2):
138-140.
7. Weng S-L, Chiu C-M, Lin F-M, Huang W-C, Liang C. Bacterial communities in semen from
men of infertile couples: metagenomic sequencing reveals relationships of seminal microbiota
to semen quality. PLoS NE 2014 9 (10): e110152.
8. Anderson A, heng , Song D, LaRosa D, Rooijen N, Kierstein G, Kierstein S, Haczku A,
Levinson1 A. The b cell super antigen Finegoldia magna protein L causes pulmonary
inflammation by a mechanism dependent on myd88 but not b cells or immunoglobulins.
Inflamm Res. 2012 61 (2): 6 – 69
9. Murphy EC, Janulczyk R, Karlsson C, Mörgelin M, Frick IM. Identification of pili on the
surface of Finegoldia magna - A Gram positive anaerobic cocci. Anaerobe 2014 27: 40-49.
10. Skwarczynski M, Totha I. Peptide-based synthetic vaccines. Chem Sci. 2016 7 (2): 842-854.
11. Doytchinova I, Flower D. VaxiJen: a server for prediction of protective antigens, tumour
antigens and subunit vaccines. BMC Bioinformatics 2007 5: 8-4.
12. Larsen J, Lund , Nielsen M. Improved method for predicting linear B cell epitopes.
Immunome Res. 2006 24: 2-2.
13. Saha S, Raghava G. AlgPred: prediction of allergenic proteins and mapping of IgE epitopes.
Nucleic Acids Res 2006 34: 202-209.
14. Vita R, arebski L, Greenbaum J, Emami H, Hoof I. The immune epitope database 2.0.
Nucleic Acids Res. 2009 38: 854-862.
15. Paul S, Arlehamn C, Scriba T, Dillon M, seroff C. Development and validation of a broad
scheme for prediction of HLA class II restricted T cell epitopes. J Immunol Methods. 2015
422: 28-34.
16. Alam N, Goldstein , ia B, Porter K, Kozakov D, Schueler-Furman . High-resolution
global peptide-protein docking using fragments-based PIPER-FlexPepDock. PLoS Comput.
Biol. 2017 13: e1005905.
17. Buchan D, Jones D. The PSIPRED protein analysis workbench: 20 years on. Nucleic Acids
Res. 2019 47: 402-407.
18. ang J, hang . I-TASSER server: new development for protein structure and function
predictions. Nucleic Acids Res. 2015 43: 174-181.
19. u D, hang . Improving the physical realism and structural accuracy of protein models by
a two-step atomic-level energy minimization. Biophys J. 2011 101: 2525-2534.
20. Lovell S, Davis I, Arendall B, Bakker P. Structure validation by Cα geometry: ϕ, ψ and Cβ
deviation. Proteins. 2003 50 (3): 7–
21. Gasteiger E, Hoogland C, Gattiker A, Duvaud S, Wilkins M. (2005). Protein identification
and analysis tools on the ExPASy server. I In: Walker J.M. (eds) The Proteomics Protocols
Handbook. Humana Press.
22. Hebditch M, Carballo-Amador MA, Charonis S, Curtis R, Warwicker J. Protein-Sol: a web
tool for predicting protein solubility from sequence. Bioinformatics 2017 33 (19): 3098-3100.
23. Puigbò P, Guzmán E, Romeu A, Garcia-Vallvé S. PTIMI ER: a web server for optimizing
the codon usage of DNA sequences. Nucleic Acids Res. 2007 35: 126-131.
24. Saha CK, Mahbub Hasan M, Hossain S, Jahan A, Azad AK. In silico identification and
characterization of common epitope-based peptide vaccine for Nipah and Hendra viruses.
Asian Pac J Trop Med 2017 10 (6): 529-538.
25. Jin , Sun T, ia , Wei , Song . ptimized expression, purification of herpes B virus GD
protein in Escherichia coli, and production of its monoclonal antibodies. Jundishapur J
Microbiol 2016 9 (3): e32183.
26. Saadi M, Karkhah A, Nouri HR. Development of a multi-epitope peptide vaccine inducing
robust T cell responses against brucellosis using immunoinformatics based approaches. Infect.
Genet. Evol. 2017 51: 227-234.
27. Stratmann T. Cholera toxin subunit B as adjuvant-an accelerator in protective immunity and a
break in autoimmunity. Vaccines 2015 3 (3): 579-596.