DOI: https://doi.org/10.14710/jbtr.v9i1.16379

Potential of B-Cell Epitopes Protein Ag85 Complex Mycobacterium Tuberculosis as Serodiagnostic Antigen of Tuberculosis by in Silico Study

1Department of Microbiology, Faculty of Medicine, University of Jember, Indonesia

2Department of Histology, Faculty of Medicine, University of Jember, Indonesia

Received: 5 Nov 2023; Revised: 16 Apr 2023; Accepted: 28 Apr 2023; Available online: 30 Apr 2023; Published: 29 Apr 2023.
Open Access Copyright (c) 2023 Journal of Biomedicine and Translational Research
Creative Commons License This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Citation Format:
Abstract

Background: The high case of tuberculosis which isn't followed by good detection becomes an urgency for the diagnostic developments. One of them with immunodiagnostic principle uses B-cell Ag85 complex epitope. The design of the diagnostic epitope was performed by mapping the B cell epitope used in silico studies.

Objective: The purpose of this research is to analyze antigenicity, physicochemical which affect immunogenicity, and homology of B-cell Ag85 complex epitope with the strain which circulates in Indonesia.  

Methods: The samples used were taken from the NCBI protein bank with access numbers P9WQP3 for Ag85A, P9WQP1 for Ag85B, and P9WQN9 for Ag85C. The sequences were analyzed using IEDB (Bepipred) software as the epitope prediction, VaxiJen as antigenicity prediction, ProtParam as physicochemical properties prediction, and BLASTP NCBI as sequence alignment.

Results: Twenty seven epitopes were antigenic with 0.4297 to 2.6007 scores and the molecular weight was from 619.59 Da to 3145.36 Da. This research also obtained eleven stable and hydrophilic epitopes. The alignment of 11 candidate epitopes with the strain which circulates in Indonesia, had a similarity percentage of 85.71%-100% and 3 epitopes had a more significant score.

Conclusion: Three epitopes of Ag85 complex; Ag85A (212-235), Ag85B (209-237), and Ag85C (283-310), were universal antigens and can be developed into diagnostic antigens in Indonesia.

 

Note: This article has supplementary file(s).

Fulltext View|Download |  Cover Letter
Submission Letter
Subject
Type Cover Letter
  Download (53KB)    Indexing metadata
 Copyright Transfer Agreement
Conflict of Interest Declaration and Copyright Transfer Agreement
Subject
Type Copyright Transfer Agreement
  Download (47KB)    Indexing metadata
Keywords: B-cell epitope; Ag85 complex; diagnostic antigen; in silico;

Article Metrics:

Article Info
Section: Original Research Articles
Language : EN
Recent articles
Effect of Probiotic Supplementation on FSH, LH Levels and Folliculogenesis Renoprotective Effect Of Sambiloto (Andrographis Paniculata) Leaf Extract On Lipopolysaccharide – Induced Septic Rats The Effect of Liprotide-Encapsulated Vitamin D3 on MDA and SOD in Rats Deficient Vitamin D and Calcium Understanding Platelet-Rich Plasma as Potential Therapy To Improve Cardiac Function After Myocardial Infarction: Based On Evidence More recent articles
  1. WHO. TB burden report 2018 [Internet]. Vol. 63, World Health Organization. 2018. 476 p. Available from: https://apps.who.int/iris/handle/10665/274453
  2. KEMENKES RI. Profil Kesehatan Indonesia 2020 [Internet]. Kementrian Kesehatan Republik Indonesia. 2021. 139 p. Available from: https://pusdatin.kemkes.go.id/resources/download/pusdatin/profil-kesehatan-indonesia/Profil-Kesehatan-Indonesia-Tahun-2020.pdf
  3. Karbalaei M, Soleimanpour S, Rezaee SA. Antigen 85 complex as a powerful Mycobacterium tuberculosis immunogene: Biology, immune-pathogenicity, applications in diagnosis, and vaccine design. Microb Pathog [Internet]. 2017;112:20–9. Available from: https://doi.org/10.1016/j.micpath.2017.08.040
  4. Huygen K. The immunodominant T-cell epitopes of the mycolyl-transferases of the antigen 85 complex of M. tuberculosis. Front Immunol [Internet]. 2014;5:1–11. Available from: https://doi.org/10.3389/fimmu.2014.00321
  5. Steingart KR, Flores LL, Dendukuri N, Schiller I, Laal S, Ramsay A, et al. Commercial Serological tests for the diagnosis of active pulmonary and extrapulmonary tuberculosis: An updated systematic review and Meta-Analysis. PLoS Med [Internet]. 2011;8. Available from: https://doi.org/10.1371/journal.pmed.1001062
  6. Carmona SJ, Sartor PA, Leguizamón MS, Campetella OE, Agüero F. Diagnostic Peptide Discovery: Prioritization of Pathogen Diagnostic Markers Using Multiple Features. PLoS One [Internet]. 2012;7. Available from: https://doi.org/10.1371/journal.pone.0050748
  7. Goyal B, Kumar K, Gupta D, Agarwal R, Latawa R, Sheikh JA, et al. Utility of B-cell epitopes based peptides of RD1 and RD2 antigens for immunodiagnosis of pulmonary tuberculosis. Diagn Microbiol Infect Dis [Internet]. 2014;78:391–7. Available from: http://dx.doi.org/10.1016/j.diagmicrobio.2013.12.018
  8. Bundschuh C, Egger M, Wiesinger K, Gabriel C, Clodi M, Mueller T, et al. Evaluation of the EDI enzyme linked immunosorbent assays for the detection of SARS-CoV-2 IgM and IgG antibodies in human plasma. Clin Chim Acta [Internet]. 2020;509:79–82. Available from: https://doi.org/10.1016/j.cca.2020.05.047
  9. Hong SC, Chen H, Lee J, Park HK, Kim YS, Shin HC, et al. Ultrasensitive immunosensing of tuberculosis CFP-10 based on SPR spectroscopy. Sensors Actuators, B Chem [Internet]. 2011;156:271–5. Available from: http://dx.doi.org/10.1016/j.snb.2011.04.032
  10. Dimitrov I, Atanasova M, Patronov A, Flower DR, Doytchinova I. A cohesive and integrated platform for immunogenicity prediction. Methods Mol Biol [Internet]. 2016;1404:761–70. Available from: https://doi.org/10.1007/978-1-4939-3389-1_50
  11. Larsen JEP, Lund O, Nielsen M. Improved method for predicting linear B-cell epitopes. Immunome Res [Internet]. 2006;2:2. Available from: https://doi.org/10.1186/1745-7580-2-2
  12. Abbas AK, Lichtman AH, Pillai S. Cellular and Molecular Immunology E-Book [Internet]. 8th ed. California: Elsevier Health Sciences; 2014. Available from: https://books.google.co.id/books?id=RWYWBAAAQBAJ
  13. Jacobs AJ, Mongkolsapaya J, Screaton GR, McShane H, Wilkinson RJ. Antibodies and tuberculosis. Tuberculosis [Internet]. 2016;101:102–13. Available from: http://dx.doi.org/10.1016/j.tube.2016.08.001
  14. Kumar G, Dagur PK, Singh M, Yadav VS, Dayal R, Singh HB, et al. Diagnostic potential of Ag85C in comparison to various secretory antigens for childhood tuberculosis. Scand J Immunol [Internet]. 2008;68:177–83. Available from: https://doi.org/10.1111/j.1365-3083.2008.02133.x
  15. Mani V, Paleja B, Larbi K, Kumar P, Tay JA, Siew JY, et al. Microchip-based ultrafast serodiagnostic assay for tuberculosis. Sci Rep [Internet]. 2016;6:1–11. Available from: https://doi.org/10.1038/srep35845
  16. Lily Therese K, Gayathri R, Dhanurekha L, Sridhar R, Meenakshi N, Madhavan HN, et al. Detection of Mycobacterium tuberculosis directly from sputum specimens & phenotypic drug resistance pattern of M. tuberculosis isolates from suspected tuberculosis patients in Chennai. Indian J Med Res [Internet]. 2012;135:778–82. Available from: pmid: 22771612
  17. Hajissa K, Zakaria R, Suppian R, Mohamed Z. Design and evaluation of a recombinant multi-epitope antigen for serodiagnosis of Toxoplasma gondii infection in humans. Parasites and Vectors [Internet]. 2015;8:1–5. Available from: https://doi.org/10.1186/s13071-015-0932-0
  18. Ebrahimipour M, Afgar A, Barati M, Mohammadi MA, Harandi MF. Evaluation of the antigenic epitopes of EgAgB/1 and EgAgB/4 subunit antigens in G1 and G6 genotypes of Echinococcus granulosus using bioinformatics. Gene Reports [Internet]. 2019;15:100361. Available from: https://doi.org/10.1016/j.genrep.2019.01.002
  19. Ebrahimi M, Seyyedtabaei SJ, Ranjbar MM, Tahvildar-biderouni F, Javadi Mamaghani A. Designing and Modeling of Multi-epitope Proteins for Diagnosis of Toxocara canis Infection. Int J Pept Res Ther [Internet]. 2020;26:1371–80. Available from: https://doi.org/10.1007/s10989-019-09940-1
  20. Mahboobi M, Sedighian H, Malekara E, Khalili S, Rahbar MR, Ahmadi Zanoos K, et al. Harnessing an Integrative In Silico Approach to Engage Highly Immunogenic Peptides in an Antigen Design Against Epsilon Toxin (ETX) of Clostridium perfringens. Int J Pept Res Ther [Internet]. 2021;27:1019–
  21. Available from: https://doi.org/10.1007/s10989-020-10147-y
  22. Suardana IBK. Diktat Imunologi Dasar Sistem Imun. 2017;1–36. Available from: https://simdos.unud.ac.id/uploads/file_pendidikan_1_dir/284a0e69155751dc6c459b07f14bc03c.pdf
  23. Shen G, Behera D, Bhalla M, Nadas A, Laal S. Peptide-based antibody detection for tuberculosis diagnosis. Clin Vaccine Immunol. 2009;16:49–54
  24. Scheiblhofer S, Laimer J, Machado Y, Weiss R, Thalhamer J. Influence of protein fold stability on immunogenicity and its implications for vaccine design. Expert Rev Vaccines [Internet]
  25. ;16:479–89. Available from: https://doi.org/10.1080/14760584.2017.1306441
  26. MacHado Y, Freier R, Scheiblhofer S, Thalhamer T, Mayr M, Briza P, et al. Fold stability during endolysosomal acidification is a key factor for allergenicity and immunogenicity of the major birch pollen allergen. J Allergy Clin Immunol [Internet]. 2016;137:1525–34. Available from: http://dx.doi.org/10.1016/j.jaci.2015.09.026
  27. Thalhamer T, Dobias H, Stepanoska T, Pröll M, Stutz H, Dissertori O, et al. Designing hypoallergenic derivatives for allergy treatment by means of in silico mutation and screening. J Allergy Clin Immunol [Internet]. 2010;125. Available from: http://dx.doi.org/10.1016/j.jaci.2010.01.031
  28. Subekti D, Artama W, Poerwanto S, Sulistyaningsih E, Sari Y. Analisis Imunogenitas Protein GRA1 dari Hasil Kloning Gen GRA 1 Takizoit Toxoplasma gondi. 2012;11
  29. Ahmad B, Ashfaq UA, Rahman M ur, Masoud MS, Yousaf MZ. Conserved B and T cell epitopes prediction of ebola virus glycoprotein for vaccine development: An immuno-informatics approach. Microb Pathog [Internet]. 2019;132:243–53. Available from: https://doi.org/10.1016/j.micpath.2019.05.010
  30. Narayanan S, Deshpande U. Whole-genome sequences of four clinical isolates of Mycobacterium tuberculosis from Tamil Nadu, south India. Genome Announc [Internet]. 2013;1:4430. Available from: https://doi.org/10.1128/genomeA.00186-13
  31. Joshi T, Xu D. Quantitative assessment of relationship between sequence similarity and function similarity. BMC Genomics [Internet]. 2007;8:1–10. Available from: https://doi.org/10.1186/1471-2164-8-222
  32. Fassler J, Cooper P. BLAST Glossary. 2011;1–8

Last update:

No citation recorded.

Last update:

No citation recorded.