Innovative epitopes in Staphylococcal Protein-A an immuno-informatics approach to combat MDR-MRSA infections

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge in clinical environments due to its resistance to standard antibiotics. Staphylococcal Protein A (SpA), a crucial virulence factor of MRSA, undermines host immune responses, making it an attractive target for...

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Main Authors: Pengjun Zhou, Xing Shi, Jinquan Xia, Yifei Wang, Shaowei Dong
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2024.1503944/full
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author Pengjun Zhou
Pengjun Zhou
Xing Shi
Jinquan Xia
Yifei Wang
Shaowei Dong
author_facet Pengjun Zhou
Pengjun Zhou
Xing Shi
Jinquan Xia
Yifei Wang
Shaowei Dong
author_sort Pengjun Zhou
collection DOAJ
description BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge in clinical environments due to its resistance to standard antibiotics. Staphylococcal Protein A (SpA), a crucial virulence factor of MRSA, undermines host immune responses, making it an attractive target for vaccine development. This study aimed to identify potential epitopes within SpA that could elicit robust immune responses, ultimately contributing to the combat against multidrug-resistant (MDR) MRSA.MethodsThe SpA protein sequence was retrieved from the UniProt database, with various bioinformatics tools employed for epitope prediction. T-cell epitopes were identified using the Tepitool server, focusing on high-affinity interactions with prevalent human leukocyte antigens (HLAs). B-cell epitopes were predicted using the BepiPred tool. Predicted epitopes underwent docking studies with HLA molecules to evaluate binding properties. In-silico analyses confirmed the antigenicity, promiscuity, and non-glycosylated nature of the selected epitopes.ResultsSeveral T and B cell epitopes within SpA were identified, showcasing high binding affinities and extensive population coverage. A multi-epitope vaccine construct, linked by synthetic linkers and an adjuvant, was modelled, refined, and validated through various bioinformatics assessments. The vaccine candidate was subsequently docked with Toll-like receptor 4 (TLR-4) to evaluate its potential for immunogenicity.ConclusionThis study lays the groundwork for developing epitope-based vaccines targeting SpA in MRSA, identifying promising candidates for experimental validation and contributing to innovative immunotherapeutic strategies against MRSA infections.
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spelling doaj-art-5ca4d58245024a198e150f53183abf7c2025-01-14T06:10:35ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-01-011410.3389/fcimb.2024.15039441503944Innovative epitopes in Staphylococcal Protein-A an immuno-informatics approach to combat MDR-MRSA infectionsPengjun Zhou0Pengjun Zhou1Xing Shi2Jinquan Xia3Yifei Wang4Shaowei Dong5Department of Pharmacology, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, ChinaDepartment of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, ChinaGuangzhou Jinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, ChinaBackgroundMethicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge in clinical environments due to its resistance to standard antibiotics. Staphylococcal Protein A (SpA), a crucial virulence factor of MRSA, undermines host immune responses, making it an attractive target for vaccine development. This study aimed to identify potential epitopes within SpA that could elicit robust immune responses, ultimately contributing to the combat against multidrug-resistant (MDR) MRSA.MethodsThe SpA protein sequence was retrieved from the UniProt database, with various bioinformatics tools employed for epitope prediction. T-cell epitopes were identified using the Tepitool server, focusing on high-affinity interactions with prevalent human leukocyte antigens (HLAs). B-cell epitopes were predicted using the BepiPred tool. Predicted epitopes underwent docking studies with HLA molecules to evaluate binding properties. In-silico analyses confirmed the antigenicity, promiscuity, and non-glycosylated nature of the selected epitopes.ResultsSeveral T and B cell epitopes within SpA were identified, showcasing high binding affinities and extensive population coverage. A multi-epitope vaccine construct, linked by synthetic linkers and an adjuvant, was modelled, refined, and validated through various bioinformatics assessments. The vaccine candidate was subsequently docked with Toll-like receptor 4 (TLR-4) to evaluate its potential for immunogenicity.ConclusionThis study lays the groundwork for developing epitope-based vaccines targeting SpA in MRSA, identifying promising candidates for experimental validation and contributing to innovative immunotherapeutic strategies against MRSA infections.https://www.frontiersin.org/articles/10.3389/fcimb.2024.1503944/fullhuman leukocyte antigenimmuno-informaticsmethicillin-resistant Staphylococcus aureusStaphylococcal Protein Atoll-like receptorvaccine development
spellingShingle Pengjun Zhou
Pengjun Zhou
Xing Shi
Jinquan Xia
Yifei Wang
Shaowei Dong
Innovative epitopes in Staphylococcal Protein-A an immuno-informatics approach to combat MDR-MRSA infections
Frontiers in Cellular and Infection Microbiology
human leukocyte antigen
immuno-informatics
methicillin-resistant Staphylococcus aureus
Staphylococcal Protein A
toll-like receptor
vaccine development
title Innovative epitopes in Staphylococcal Protein-A an immuno-informatics approach to combat MDR-MRSA infections
title_full Innovative epitopes in Staphylococcal Protein-A an immuno-informatics approach to combat MDR-MRSA infections
title_fullStr Innovative epitopes in Staphylococcal Protein-A an immuno-informatics approach to combat MDR-MRSA infections
title_full_unstemmed Innovative epitopes in Staphylococcal Protein-A an immuno-informatics approach to combat MDR-MRSA infections
title_short Innovative epitopes in Staphylococcal Protein-A an immuno-informatics approach to combat MDR-MRSA infections
title_sort innovative epitopes in staphylococcal protein a an immuno informatics approach to combat mdr mrsa infections
topic human leukocyte antigen
immuno-informatics
methicillin-resistant Staphylococcus aureus
Staphylococcal Protein A
toll-like receptor
vaccine development
url https://www.frontiersin.org/articles/10.3389/fcimb.2024.1503944/full
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