A Chimeric Vaccine Consisting of Highly Immunogenic Regions Form Escherichia coli Iron Regulated Outer-Membrane Proteins: An In Silico Approach

Background: Six pathogen-associated Outer Membrane Iron receptors (OMPs) reside in Uropathogenic strains of E. coli (UPEC): haem-utilization gene (ChuA), Heme acquisition protein (Hma), IrgA homologue adhesin (Iha), Iron-regulated virulence gene (IreA), IroN, and IutA. Cumulative concern over the pr...

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Main Authors: Fatemeh Sefid, Mahsa Akbari Oryani, Maryam Mehdi, Zahra Payandeh, Saeed Khalili, Ehsan Kaffash, Ghasem Azamirad, Seyed Mehdi Kalantar
Format: Article
Language:English
Published: Mazandaran University of Medical Sciences and Health Services 2021-05-01
Series:Research in Molecular Medicine
Subjects:
Online Access:http://rmm.mazums.ac.ir/article-1-411-en.html
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author Fatemeh Sefid
Mahsa Akbari Oryani
Maryam Mehdi
Zahra Payandeh
Saeed Khalili
Ehsan Kaffash
Ghasem Azamirad
Seyed Mehdi Kalantar
author_facet Fatemeh Sefid
Mahsa Akbari Oryani
Maryam Mehdi
Zahra Payandeh
Saeed Khalili
Ehsan Kaffash
Ghasem Azamirad
Seyed Mehdi Kalantar
author_sort Fatemeh Sefid
collection DOAJ
description Background: Six pathogen-associated Outer Membrane Iron receptors (OMPs) reside in Uropathogenic strains of E. coli (UPEC): haem-utilization gene (ChuA), Heme acquisition protein (Hma), IrgA homologue adhesin (Iha), Iron-regulated virulence gene (IreA), IroN, and IutA. Cumulative concern over the prevalence of this bacteria in hospital environments, especially in Intensive Care Units (ICUs), highlights the significance of vaccination against this pathogen. In this study, we aimed to develop 3D models of ChuA, Hma, IutA, IreA, Iha, and IroN proteins by invoking various in silico methods and design a chimeric immunogen composed of highly immunogenic regions from these six Escherichia coli antigens as a chimeric vaccine. Materials and Methods: In the present study, homology modeling, fold recognition, Ab initio approaches, and their combination were invoked to determine the Three-Dimensional (3D) structures of ChuA, Hma, Iha, IreA, IroN, and IutA. Next, a set of biochemical, immunological, and functional properties were predicted using various bioinformatics tools. Results: The obtained results indicated that all six modeled proteins fold to a β-barrel structure. The results of biochemical, immunological, and functional analysis determined the regions of each antigen carrying the best immunogenic properties. These regions are employed to construct the final vaccine linked via flexible GGGGS linkers. Intriguingly, re-analyzing the properties of the final vaccine indicated its immunological advantage over individual proteins.  Conclusion: The strategy of this study to predict the protein 3D structure, followed by epitope prediction, could be adapted to design efficient vaccine candidates. Applying this approach, we designed a vaccine candidate harboring the most promising regions of six OMPs. This approach could lead to better functional, structural, and therapeutic outcomes in the context of vaccine design investigations.
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spelling doaj.art-fc9ecc11d56f4c17bc7be33fb00ca06e2023-01-01T05:41:45ZengMazandaran University of Medical Sciences and Health ServicesResearch in Molecular Medicine2322-13482322-133X2021-05-0192119138A Chimeric Vaccine Consisting of Highly Immunogenic Regions Form Escherichia coli Iron Regulated Outer-Membrane Proteins: An In Silico ApproachFatemeh Sefid0Mahsa Akbari Oryani1Maryam Mehdi2Zahra Payandeh3Saeed Khalili4Ehsan Kaffash5Ghasem Azamirad6Seyed Mehdi Kalantar7 Department of Biology Sciences, School of Materials Engineering and Interdisciplinary Sciences, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Department of Pathology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Department of Mechanical Engineering, Yazd University, Yazd, Iran. Department of Medical Genetics, Shahid Sadoughi University of Medical Science, Yazd, Iran. Background: Six pathogen-associated Outer Membrane Iron receptors (OMPs) reside in Uropathogenic strains of E. coli (UPEC): haem-utilization gene (ChuA), Heme acquisition protein (Hma), IrgA homologue adhesin (Iha), Iron-regulated virulence gene (IreA), IroN, and IutA. Cumulative concern over the prevalence of this bacteria in hospital environments, especially in Intensive Care Units (ICUs), highlights the significance of vaccination against this pathogen. In this study, we aimed to develop 3D models of ChuA, Hma, IutA, IreA, Iha, and IroN proteins by invoking various in silico methods and design a chimeric immunogen composed of highly immunogenic regions from these six Escherichia coli antigens as a chimeric vaccine. Materials and Methods: In the present study, homology modeling, fold recognition, Ab initio approaches, and their combination were invoked to determine the Three-Dimensional (3D) structures of ChuA, Hma, Iha, IreA, IroN, and IutA. Next, a set of biochemical, immunological, and functional properties were predicted using various bioinformatics tools. Results: The obtained results indicated that all six modeled proteins fold to a β-barrel structure. The results of biochemical, immunological, and functional analysis determined the regions of each antigen carrying the best immunogenic properties. These regions are employed to construct the final vaccine linked via flexible GGGGS linkers. Intriguingly, re-analyzing the properties of the final vaccine indicated its immunological advantage over individual proteins.  Conclusion: The strategy of this study to predict the protein 3D structure, followed by epitope prediction, could be adapted to design efficient vaccine candidates. Applying this approach, we designed a vaccine candidate harboring the most promising regions of six OMPs. This approach could lead to better functional, structural, and therapeutic outcomes in the context of vaccine design investigations.http://rmm.mazums.ac.ir/article-1-411-en.htmlurinary tract infectionsvaccineiron receptorbioinformaticsouter membrane protein (omp)
spellingShingle Fatemeh Sefid
Mahsa Akbari Oryani
Maryam Mehdi
Zahra Payandeh
Saeed Khalili
Ehsan Kaffash
Ghasem Azamirad
Seyed Mehdi Kalantar
A Chimeric Vaccine Consisting of Highly Immunogenic Regions Form Escherichia coli Iron Regulated Outer-Membrane Proteins: An In Silico Approach
Research in Molecular Medicine
urinary tract infections
vaccine
iron receptor
bioinformatics
outer membrane protein (omp)
title A Chimeric Vaccine Consisting of Highly Immunogenic Regions Form Escherichia coli Iron Regulated Outer-Membrane Proteins: An In Silico Approach
title_full A Chimeric Vaccine Consisting of Highly Immunogenic Regions Form Escherichia coli Iron Regulated Outer-Membrane Proteins: An In Silico Approach
title_fullStr A Chimeric Vaccine Consisting of Highly Immunogenic Regions Form Escherichia coli Iron Regulated Outer-Membrane Proteins: An In Silico Approach
title_full_unstemmed A Chimeric Vaccine Consisting of Highly Immunogenic Regions Form Escherichia coli Iron Regulated Outer-Membrane Proteins: An In Silico Approach
title_short A Chimeric Vaccine Consisting of Highly Immunogenic Regions Form Escherichia coli Iron Regulated Outer-Membrane Proteins: An In Silico Approach
title_sort chimeric vaccine consisting of highly immunogenic regions form escherichia coli iron regulated outer membrane proteins an in silico approach
topic urinary tract infections
vaccine
iron receptor
bioinformatics
outer membrane protein (omp)
url http://rmm.mazums.ac.ir/article-1-411-en.html
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