Core-genome-mediated promising alternative drug and multi-epitope vaccine targets prioritization against infectious Clostridium difficile
Prevention of Clostridium difficile infection is challenging worldwide owing to its high morbidity and mortality rates. C. difficile is currently being classified as an urgent threat by the CDC. Devising a new therapeutic strategy become indispensable against C. difficile infection due to its high r...
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| creator | Aiman, Sara Farooq, Qurrat Ul Ain Han, Zhongjie Aslam, Muneeba Zhang, Jilong Khan, Asifullah Ahmad, Abbas Li, Chunhua Ali, Yasir |
| description | Prevention of Clostridium difficile infection is challenging worldwide owing to its high morbidity and mortality rates. C. difficile is currently being classified as an urgent threat by the CDC. Devising a new therapeutic strategy become indispensable against C. difficile infection due to its high rates of reinfection and increasing antimicrobial resistance. The current study is based on core proteome data of C. difficile to identify promising vaccine and drug candidates. Immunoinformatics and vaccinomics approaches were employed to construct multi-epitope-based chimeric vaccine constructs from top-ranked T- and B-cell epitopes. The efficacy of the designed vaccine was assessed by immunological analysis, immune receptor binding potential and immune simulation analyses. Additionally, subtractive proteomics and druggability analyses prioritized several promising and alternative drug targets against C. difficile. These include FMN-dependent nitroreductase which was prioritized for pharmacophore-based virtual screening of druggable molecule databases to predict potent inhibitors. A MolPort-001-785-965 druggable molecule was found to exhibit significant binding affinity with the conserved residues of FMN-dependent nitroreductase. The experimental validation of the therapeutic targets prioritized in the current study may worthy to identify new strategies to combat the drug-resistant C. difficile infection. |
| doi_str_mv | 10.1371/journal.pone.0293731 |
| format | Article |
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C. difficile is currently being classified as an urgent threat by the CDC. Devising a new therapeutic strategy become indispensable against C. difficile infection due to its high rates of reinfection and increasing antimicrobial resistance. The current study is based on core proteome data of C. difficile to identify promising vaccine and drug candidates. Immunoinformatics and vaccinomics approaches were employed to construct multi-epitope-based chimeric vaccine constructs from top-ranked T- and B-cell epitopes. The efficacy of the designed vaccine was assessed by immunological analysis, immune receptor binding potential and immune simulation analyses. Additionally, subtractive proteomics and druggability analyses prioritized several promising and alternative drug targets against C. difficile. These include FMN-dependent nitroreductase which was prioritized for pharmacophore-based virtual screening of druggable molecule databases to predict potent inhibitors. A MolPort-001-785-965 druggable molecule was found to exhibit significant binding affinity with the conserved residues of FMN-dependent nitroreductase. The experimental validation of the therapeutic targets prioritized in the current study may worthy to identify new strategies to combat the drug-resistant C. difficile infection.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0293731</identifier><identifier>PMID: 38241420</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Antibiotics ; Antigenic determinants ; Antimicrobial resistance ; B cells ; Bacterial proteins ; Binding ; Biofilms ; Care and treatment ; Clostridium difficile ; Clostridium infections ; Complications and side effects ; Contamination ; Design ; Dosage and administration ; Drug development ; Drug resistance ; Drug resistance in microorganisms ; Epitopes ; Genomes ; Genomics ; Health aspects ; Imipenem ; Immunology ; Infection ; Lymphocytes B ; Medical research ; Medicine, Experimental ; Morbidity ; Mortality ; Nitroreductase ; Nosocomial infections ; Pathogens ; Peptides ; Prevention ; Proteomes ; Proteomics ; Rankings ; Tetracycline ; Tetracyclines ; Therapeutic targets ; Toxicity ; Toxins ; United Kingdom ; Vaccines ; Viral vaccines</subject><ispartof>PloS one, 2024-01, Vol.19 (1), p.e0293731-e0293731</ispartof><rights>Copyright: © 2024 Aiman et al. 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Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c586t-8f954531e5e589ba2797313e701a259641efb02a668ee3e27329b5a864a8ecb63</cites><orcidid>0000-0001-8895-7808</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0293731&type=printable$$EPDF$$P50$$Gplos$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0293731$$EHTML$$P50$$Gplos$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,860,2096,2915,23845,27901,27902,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38241420$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aiman, Sara</creatorcontrib><creatorcontrib>Farooq, Qurrat Ul Ain</creatorcontrib><creatorcontrib>Han, Zhongjie</creatorcontrib><creatorcontrib>Aslam, Muneeba</creatorcontrib><creatorcontrib>Zhang, Jilong</creatorcontrib><creatorcontrib>Khan, Asifullah</creatorcontrib><creatorcontrib>Ahmad, Abbas</creatorcontrib><creatorcontrib>Li, Chunhua</creatorcontrib><creatorcontrib>Ali, Yasir</creatorcontrib><title>Core-genome-mediated promising alternative drug and multi-epitope vaccine targets prioritization against infectious Clostridium difficile</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Prevention of Clostridium difficile infection is challenging worldwide owing to its high morbidity and mortality rates. C. difficile is currently being classified as an urgent threat by the CDC. Devising a new therapeutic strategy become indispensable against C. difficile infection due to its high rates of reinfection and increasing antimicrobial resistance. The current study is based on core proteome data of C. difficile to identify promising vaccine and drug candidates. Immunoinformatics and vaccinomics approaches were employed to construct multi-epitope-based chimeric vaccine constructs from top-ranked T- and B-cell epitopes. The efficacy of the designed vaccine was assessed by immunological analysis, immune receptor binding potential and immune simulation analyses. Additionally, subtractive proteomics and druggability analyses prioritized several promising and alternative drug targets against C. difficile. These include FMN-dependent nitroreductase which was prioritized for pharmacophore-based virtual screening of druggable molecule databases to predict potent inhibitors. 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The experimental validation of the therapeutic targets prioritized in the current study may worthy to identify new strategies to combat the drug-resistant C. difficile infection.</description><subject>Analysis</subject><subject>Antibiotics</subject><subject>Antigenic determinants</subject><subject>Antimicrobial resistance</subject><subject>B cells</subject><subject>Bacterial proteins</subject><subject>Binding</subject><subject>Biofilms</subject><subject>Care and treatment</subject><subject>Clostridium difficile</subject><subject>Clostridium infections</subject><subject>Complications and side effects</subject><subject>Contamination</subject><subject>Design</subject><subject>Dosage and administration</subject><subject>Drug development</subject><subject>Drug resistance</subject><subject>Drug resistance in microorganisms</subject><subject>Epitopes</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Health 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C. difficile is currently being classified as an urgent threat by the CDC. Devising a new therapeutic strategy become indispensable against C. difficile infection due to its high rates of reinfection and increasing antimicrobial resistance. The current study is based on core proteome data of C. difficile to identify promising vaccine and drug candidates. Immunoinformatics and vaccinomics approaches were employed to construct multi-epitope-based chimeric vaccine constructs from top-ranked T- and B-cell epitopes. The efficacy of the designed vaccine was assessed by immunological analysis, immune receptor binding potential and immune simulation analyses. Additionally, subtractive proteomics and druggability analyses prioritized several promising and alternative drug targets against C. difficile. These include FMN-dependent nitroreductase which was prioritized for pharmacophore-based virtual screening of druggable molecule databases to predict potent inhibitors. A MolPort-001-785-965 druggable molecule was found to exhibit significant binding affinity with the conserved residues of FMN-dependent nitroreductase. The experimental validation of the therapeutic targets prioritized in the current study may worthy to identify new strategies to combat the drug-resistant C. difficile infection.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>38241420</pmid><doi>10.1371/journal.pone.0293731</doi><tpages>e0293731</tpages><orcidid>https://orcid.org/0000-0001-8895-7808</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis Antibiotics Antigenic determinants Antimicrobial resistance B cells Bacterial proteins Binding Biofilms Care and treatment Clostridium difficile Clostridium infections Complications and side effects Contamination Design Dosage and administration Drug development Drug resistance Drug resistance in microorganisms Epitopes Genomes Genomics Health aspects Imipenem Immunology Infection Lymphocytes B Medical research Medicine, Experimental Morbidity Mortality Nitroreductase Nosocomial infections Pathogens Peptides Prevention Proteomes Proteomics Rankings Tetracycline Tetracyclines Therapeutic targets Toxicity Toxins United Kingdom Vaccines Viral vaccines |
| title | Core-genome-mediated promising alternative drug and multi-epitope vaccine targets prioritization against infectious Clostridium difficile |
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