Proteome level analysis of drug-resistant Prevotella melaninogenica for the identification of novel therapeutic candidates
The management of infectious diseases has become more critical due to the development of novel pathogenic strains with enhanced resistance. Prevotella melaninogenica, a gram-negative bacterium, was found to be involved in various infections of the respiratory tract, aerodigestive tract, and gastroin...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1271798/full |
| _version_ | 1797676920064704512 |
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| author | Mohibullah Shah Amna Anwar Aqsa Qasim Samavia Jaan Asifa Sarfraz Riaz Ullah Essam A. Ali Umar Nishan Muhammad Shehroz Aqal Zaman Suvash Chandra Ojha |
| author_facet | Mohibullah Shah Amna Anwar Aqsa Qasim Samavia Jaan Asifa Sarfraz Riaz Ullah Essam A. Ali Umar Nishan Muhammad Shehroz Aqal Zaman Suvash Chandra Ojha |
| author_sort | Mohibullah Shah |
| collection | DOAJ |
| description | The management of infectious diseases has become more critical due to the development of novel pathogenic strains with enhanced resistance. Prevotella melaninogenica, a gram-negative bacterium, was found to be involved in various infections of the respiratory tract, aerodigestive tract, and gastrointestinal tract. The need to explore novel drug and vaccine targets against this pathogen was triggered by the emergence of antimicrobial resistance against reported antibiotics to combat P. melaninogenica infections. The study involves core genes acquired from 14 complete P. melaninogenica strain genome sequences, where promiscuous drug and vaccine candidates were explored by state-of-the-art subtractive proteomics and reverse vaccinology approaches. A stringent bioinformatics analysis enlisted 18 targets as novel, essential, and non-homologous to humans and having druggability potential. Moreover, the extracellular and outer membrane proteins were subjected to antigenicity, allergenicity, and physicochemical analysis for the identification of the candidate proteins to design multi-epitope vaccines. Two candidate proteins (ADK95685.1 and ADK97014.1) were selected as the best target for the designing of a vaccine construct. Lead B- and T-cell overlapped epitopes were joined to generate potential chimeric vaccine constructs in combination with adjuvants and linkers. Finally, a prioritized vaccine construct was found to have stable interactions with the human immune cell receptors as confirmed by molecular docking and MD simulation studies. The vaccine construct was found to have cloning and expression ability in the bacterial cloning system. Immune simulation ensured the elicitation of significant immune responses against the designed vaccine. In conclusion, our study reported novel drug and vaccine targets and designed a multi-epitope vaccine against the P. melaninogenica infection. Further experimental validation will help open new avenues in the treatment of this multi-drug-resistant pathogen. |
| first_indexed | 2024-03-11T22:37:26Z |
| format | Article |
| id | doaj.art-f07e370f00684756862ef56bdba9bcae |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-03-11T22:37:26Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-f07e370f00684756862ef56bdba9bcae2023-09-22T12:56:36ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-09-011410.3389/fmicb.2023.12717981271798Proteome level analysis of drug-resistant Prevotella melaninogenica for the identification of novel therapeutic candidatesMohibullah Shah0Amna Anwar1Aqsa Qasim2Samavia Jaan3Asifa Sarfraz4Riaz Ullah5Essam A. Ali6Umar Nishan7Muhammad Shehroz8Aqal Zaman9Suvash Chandra Ojha10Department of Biochemistry, Bahauddin Zakariya University, Multan, PakistanDepartment of Biochemistry, Bahauddin Zakariya University, Multan, PakistanDepartment of Biochemistry, Bahauddin Zakariya University, Multan, PakistanDepartment of Biochemistry, Bahauddin Zakariya University, Multan, PakistanDepartment of Biochemistry, Bahauddin Zakariya University, Multan, PakistanMedicinal Aromatic and Poisonous Plants Research Center, College of Pharmacy King Saud University, Riyadh, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Chemistry, Kohat University of Science and Technology, Kohat, PakistanDepartment of Bioinformatics, Kohsar University Murree, Murree, PakistanDepartment of Microbiology and Molecular Genetics, Bahauddin Zakariya University, Multan, PakistanDepartment of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaThe management of infectious diseases has become more critical due to the development of novel pathogenic strains with enhanced resistance. Prevotella melaninogenica, a gram-negative bacterium, was found to be involved in various infections of the respiratory tract, aerodigestive tract, and gastrointestinal tract. The need to explore novel drug and vaccine targets against this pathogen was triggered by the emergence of antimicrobial resistance against reported antibiotics to combat P. melaninogenica infections. The study involves core genes acquired from 14 complete P. melaninogenica strain genome sequences, where promiscuous drug and vaccine candidates were explored by state-of-the-art subtractive proteomics and reverse vaccinology approaches. A stringent bioinformatics analysis enlisted 18 targets as novel, essential, and non-homologous to humans and having druggability potential. Moreover, the extracellular and outer membrane proteins were subjected to antigenicity, allergenicity, and physicochemical analysis for the identification of the candidate proteins to design multi-epitope vaccines. Two candidate proteins (ADK95685.1 and ADK97014.1) were selected as the best target for the designing of a vaccine construct. Lead B- and T-cell overlapped epitopes were joined to generate potential chimeric vaccine constructs in combination with adjuvants and linkers. Finally, a prioritized vaccine construct was found to have stable interactions with the human immune cell receptors as confirmed by molecular docking and MD simulation studies. The vaccine construct was found to have cloning and expression ability in the bacterial cloning system. Immune simulation ensured the elicitation of significant immune responses against the designed vaccine. In conclusion, our study reported novel drug and vaccine targets and designed a multi-epitope vaccine against the P. melaninogenica infection. Further experimental validation will help open new avenues in the treatment of this multi-drug-resistant pathogen.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1271798/fullPrevotella melaninogenicadrug targetepitopepeptide vaccineimmunoinformatics |
| spellingShingle | Mohibullah Shah Amna Anwar Aqsa Qasim Samavia Jaan Asifa Sarfraz Riaz Ullah Essam A. Ali Umar Nishan Muhammad Shehroz Aqal Zaman Suvash Chandra Ojha Proteome level analysis of drug-resistant Prevotella melaninogenica for the identification of novel therapeutic candidates Frontiers in Microbiology Prevotella melaninogenica drug target epitope peptide vaccine immunoinformatics |
| title | Proteome level analysis of drug-resistant Prevotella melaninogenica for the identification of novel therapeutic candidates |
| title_full | Proteome level analysis of drug-resistant Prevotella melaninogenica for the identification of novel therapeutic candidates |
| title_fullStr | Proteome level analysis of drug-resistant Prevotella melaninogenica for the identification of novel therapeutic candidates |
| title_full_unstemmed | Proteome level analysis of drug-resistant Prevotella melaninogenica for the identification of novel therapeutic candidates |
| title_short | Proteome level analysis of drug-resistant Prevotella melaninogenica for the identification of novel therapeutic candidates |
| title_sort | proteome level analysis of drug resistant prevotella melaninogenica for the identification of novel therapeutic candidates |
| topic | Prevotella melaninogenica drug target epitope peptide vaccine immunoinformatics |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1271798/full |
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