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In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis Infection

BACKGROUND: Latent tuberculosis infection (LTBI) is the primary source of active tuberculosis (ATB), but there are no specific methods for diagnosing and preventing LTBI. METHODS: Dominant T and B cell epitopes predicted from five antigens related to LTBI and Mycobacterium tuberculosis region of dif...

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Autores principales: Cheng, Peng, Wang, Liang, Gong, Wenping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273951/
https://www.ncbi.nlm.nih.gov/pubmed/35836423
http://dx.doi.org/10.3389/fmicb.2022.947852
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author Cheng, Peng
Wang, Liang
Gong, Wenping
author_facet Cheng, Peng
Wang, Liang
Gong, Wenping
author_sort Cheng, Peng
collection PubMed
description BACKGROUND: Latent tuberculosis infection (LTBI) is the primary source of active tuberculosis (ATB), but there are no specific methods for diagnosing and preventing LTBI. METHODS: Dominant T and B cell epitopes predicted from five antigens related to LTBI and Mycobacterium tuberculosis region of difference (LTBI-RD) were used to construct a novel polypeptide molecule (PPM). Then, the physicochemical properties, secondary structure, tertiary structure of the PPM, and its binding ability to toll-like receptor 2 (TLR2) and TLR4 were analyzed by bioinformatics tools. Finally, immune stimulation and expression optimization of the PPM were carried out. RESULTS: Four helper T lymphocytes (HTL) epitopes, five cytotoxic T lymphocytes (CTL) epitopes, and three B cell epitopes were predicted and screened from five LTBI-RD related antigens. These epitopes were connected in series with linkers and adjuvants to construct a novel PPM termed C543P. The results indicated that antigenicity and immunogenicity scores of the C543P candidate were 0.936399 and 1.36469, respectively. The structural analysis results showed that the C543P candidate had good stability. Its secondary structure contained 43.6% α-helix, the Z-score after tertiary structure optimization was −7.9, and the Ramachandran diagram showed that 88.77% amino acid residues of the C543P candidate were in the allowable region. Furthermore, the C543P candidate showed an excellent affinity to TLR2 (−1091.7kcal/mol) and TLR4 (−1102.7kcal/mol). In addition, we also analyzed the immunological characteristics of the C543P candidate. Immune stimulation prediction showed that the C543P candidate could effectively activate T and B lymphocytes and produce high levels of Th1 cytokines such as IFN-γ and IL-2. CONCLUSION: We constructed a novel PPM with acceptable antigenicity, immunogenicity, stability, and ability to induce robust immune responses. This study provides a new diagnostic biomarker or peptides-based vaccine for LTBI diagnosis and prevention.
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spelling pubmed-92739512022-07-13 In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis Infection Cheng, Peng Wang, Liang Gong, Wenping Front Microbiol Microbiology BACKGROUND: Latent tuberculosis infection (LTBI) is the primary source of active tuberculosis (ATB), but there are no specific methods for diagnosing and preventing LTBI. METHODS: Dominant T and B cell epitopes predicted from five antigens related to LTBI and Mycobacterium tuberculosis region of difference (LTBI-RD) were used to construct a novel polypeptide molecule (PPM). Then, the physicochemical properties, secondary structure, tertiary structure of the PPM, and its binding ability to toll-like receptor 2 (TLR2) and TLR4 were analyzed by bioinformatics tools. Finally, immune stimulation and expression optimization of the PPM were carried out. RESULTS: Four helper T lymphocytes (HTL) epitopes, five cytotoxic T lymphocytes (CTL) epitopes, and three B cell epitopes were predicted and screened from five LTBI-RD related antigens. These epitopes were connected in series with linkers and adjuvants to construct a novel PPM termed C543P. The results indicated that antigenicity and immunogenicity scores of the C543P candidate were 0.936399 and 1.36469, respectively. The structural analysis results showed that the C543P candidate had good stability. Its secondary structure contained 43.6% α-helix, the Z-score after tertiary structure optimization was −7.9, and the Ramachandran diagram showed that 88.77% amino acid residues of the C543P candidate were in the allowable region. Furthermore, the C543P candidate showed an excellent affinity to TLR2 (−1091.7kcal/mol) and TLR4 (−1102.7kcal/mol). In addition, we also analyzed the immunological characteristics of the C543P candidate. Immune stimulation prediction showed that the C543P candidate could effectively activate T and B lymphocytes and produce high levels of Th1 cytokines such as IFN-γ and IL-2. CONCLUSION: We constructed a novel PPM with acceptable antigenicity, immunogenicity, stability, and ability to induce robust immune responses. This study provides a new diagnostic biomarker or peptides-based vaccine for LTBI diagnosis and prevention. Frontiers Media S.A. 2022-06-28 /pmc/articles/PMC9273951/ /pubmed/35836423 http://dx.doi.org/10.3389/fmicb.2022.947852 Text en Copyright © 2022 Cheng, Wang and Gong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Cheng, Peng
Wang, Liang
Gong, Wenping
In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis Infection
title In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis Infection
title_full In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis Infection
title_fullStr In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis Infection
title_full_unstemmed In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis Infection
title_short In silico Analysis of Peptide-Based Biomarkers for the Diagnosis and Prevention of Latent Tuberculosis Infection
title_sort in silico analysis of peptide-based biomarkers for the diagnosis and prevention of latent tuberculosis infection
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273951/
https://www.ncbi.nlm.nih.gov/pubmed/35836423
http://dx.doi.org/10.3389/fmicb.2022.947852
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