An In Silico Multi-epitopes Vaccine Ensemble and Characterization Against Nosocomial Proteus penneri

Proteus penneri ( P. penneri ) is a bacillus-shaped, gram-negative, facultative anaerobe bacterium that is primarily an invasive pathogen and the etiological agent of several hospital-associated infections. P. penneri strains are naturally resistant to macrolides, amoxicillin, oxacillin, penicillin...

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Published in:Molecular biotechnology Vol. 66; no. 12; pp. 3498 - 3513
Main Authors: Ullah, Asad, Rehman, Bushra, Khan, Saifullah, Almanaa, Taghreed N., Waheed, Yasir, Hassan, Muhammad, Naz, Tahira, ul Haq, Mehboob, Muhammad, Riaz, Sanami, Samira, Irfan, Muhammad, Ahmad, Sajjad
Format: Journal Article
Language:English
Published: New York Springer US 01.12.2024
Springer Nature B.V
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ISSN:1073-6085, 1559-0305, 1559-0305
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Abstract Proteus penneri ( P. penneri ) is a bacillus-shaped, gram-negative, facultative anaerobe bacterium that is primarily an invasive pathogen and the etiological agent of several hospital-associated infections. P. penneri strains are naturally resistant to macrolides, amoxicillin, oxacillin, penicillin G, and cephalosporins; in addition, no vaccines are available against these strains. This warrants efforts to propose a theoretical based multi-epitope vaccine construct to prevent pathogen infections . In this research, reverse vaccinology bioinformatics and immunoinformatics approaches were adopted for vaccine target identification and construction of a multi-epitope vaccine. In the first phase, a core proteome dataset of the targeted pathogen was obtained using the NCBI database and subjected to bacterial pan-genome analysis using bacterial pan-genome analysis (BPGA) to predict core protein sequences which were then used to find good vaccine target candidates. This identified two proteins, Hcp family type VI secretion system effector and superoxide dismutase family protein, as promising vaccine targets. Afterward using the IEDB database, different B-cell and T-cell epitopes were predicted. A set of four epitopes “KGSVNVQDRE, NTGKLTGTR, IIHSDSWNER, and KDGKPVPALK” were chosen for the development of a multi-epitope vaccine construct. A 183 amino acid long vaccine design was built along with “EAAAK” and “GPGPG” linkers and a cholera toxin B-subunit adjuvant. The designed vaccine model comprised immunodominant, non-toxic, non-allergenic, and physicochemical stable epitopes. The model vaccine was docked with MHC-I, MHC-II, and TLR-4 immune cell receptors using the Cluspro2.0 web server. The binding energy score of the vaccine was − 654.7 kcal/mol for MHC-I, − 738.4 kcal/mol for MHC-II, and − 695.0 kcal/mol for TLR-4. A molecular dynamic simulation was done using AMBER v20 package for dynamic behavior in nanoseconds. Additionally, MM-PBSA binding free energy analysis was done to test intermolecular binding interactions between docked molecules. The MM-GBSA net binding energy score was − 148.00 kcal/mol, − 118.00 kcal/mol, and − 127.00 kcal/mol for vaccine with TLR-4, MHC-I, and MHC-II, respectively. Overall, these in silico-based predictions indicated that the vaccine is highly promising in terms of developing protective immunity against P. penneri . However, additional experimental validation is required to unveil the real immune response to the designed vaccine.
AbstractList Proteus penneri (P. penneri) is a bacillus-shaped, gram-negative, facultative anaerobe bacterium that is primarily an invasive pathogen and the etiological agent of several hospital-associated infections. P. penneri strains are naturally resistant to macrolides, amoxicillin, oxacillin, penicillin G, and cephalosporins; in addition, no vaccines are available against these strains. This warrants efforts to propose a theoretical based multi-epitope vaccine construct to prevent pathogen infections. In this research, reverse vaccinology bioinformatics and immunoinformatics approaches were adopted for vaccine target identification and construction of a multi-epitope vaccine. In the first phase, a core proteome dataset of the targeted pathogen was obtained using the NCBI database and subjected to bacterial pan-genome analysis using bacterial pan-genome analysis (BPGA) to predict core protein sequences which were then used to find good vaccine target candidates. This identified two proteins, Hcp family type VI secretion system effector and superoxide dismutase family protein, as promising vaccine targets. Afterward using the IEDB database, different B-cell and T-cell epitopes were predicted. A set of four epitopes “KGSVNVQDRE, NTGKLTGTR, IIHSDSWNER, and KDGKPVPALK” were chosen for the development of a multi-epitope vaccine construct. A 183 amino acid long vaccine design was built along with “EAAAK” and “GPGPG” linkers and a cholera toxin B-subunit adjuvant. The designed vaccine model comprised immunodominant, non-toxic, non-allergenic, and physicochemical stable epitopes. The model vaccine was docked with MHC-I, MHC-II, and TLR-4 immune cell receptors using the Cluspro2.0 web server. The binding energy score of the vaccine was − 654.7 kcal/mol for MHC-I, − 738.4 kcal/mol for MHC-II, and − 695.0 kcal/mol for TLR-4. A molecular dynamic simulation was done using AMBER v20 package for dynamic behavior in nanoseconds. Additionally, MM-PBSA binding free energy analysis was done to test intermolecular binding interactions between docked molecules. The MM-GBSA net binding energy score was − 148.00 kcal/mol, − 118.00 kcal/mol, and − 127.00 kcal/mol for vaccine with TLR-4, MHC-I, and MHC-II, respectively. Overall, these in silico-based predictions indicated that the vaccine is highly promising in terms of developing protective immunity against P. penneri. However, additional experimental validation is required to unveil the real immune response to the designed vaccine.
Proteus penneri (P. penneri) is a bacillus-shaped, gram-negative, facultative anaerobe bacterium that is primarily an invasive pathogen and the etiological agent of several hospital-associated infections. P. penneri strains are naturally resistant to macrolides, amoxicillin, oxacillin, penicillin G, and cephalosporins; in addition, no vaccines are available against these strains. This warrants efforts to propose a theoretical based multi-epitope vaccine construct to prevent pathogen infections. In this research, reverse vaccinology bioinformatics and immunoinformatics approaches were adopted for vaccine target identification and construction of a multi-epitope vaccine. In the first phase, a core proteome dataset of the targeted pathogen was obtained using the NCBI database and subjected to bacterial pan-genome analysis using bacterial pan-genome analysis (BPGA) to predict core protein sequences which were then used to find good vaccine target candidates. This identified two proteins, Hcp family type VI secretion system effector and superoxide dismutase family protein, as promising vaccine targets. Afterward using the IEDB database, different B-cell and T-cell epitopes were predicted. A set of four epitopes "KGSVNVQDRE, NTGKLTGTR, IIHSDSWNER, and KDGKPVPALK" were chosen for the development of a multi-epitope vaccine construct. A 183 amino acid long vaccine design was built along with "EAAAK" and "GPGPG" linkers and a cholera toxin B-subunit adjuvant. The designed vaccine model comprised immunodominant, non-toxic, non-allergenic, and physicochemical stable epitopes. The model vaccine was docked with MHC-I, MHC-II, and TLR-4 immune cell receptors using the Cluspro2.0 web server. The binding energy score of the vaccine was - 654.7 kcal/mol for MHC-I, - 738.4 kcal/mol for MHC-II, and - 695.0 kcal/mol for TLR-4. A molecular dynamic simulation was done using AMBER v20 package for dynamic behavior in nanoseconds. Additionally, MM-PBSA binding free energy analysis was done to test intermolecular binding interactions between docked molecules. The MM-GBSA net binding energy score was - 148.00 kcal/mol, - 118.00 kcal/mol, and - 127.00 kcal/mol for vaccine with TLR-4, MHC-I, and MHC-II, respectively. Overall, these in silico-based predictions indicated that the vaccine is highly promising in terms of developing protective immunity against P. penneri. However, additional experimental validation is required to unveil the real immune response to the designed vaccine.
Proteus penneri ( P. penneri ) is a bacillus-shaped, gram-negative, facultative anaerobe bacterium that is primarily an invasive pathogen and the etiological agent of several hospital-associated infections. P. penneri strains are naturally resistant to macrolides, amoxicillin, oxacillin, penicillin G, and cephalosporins; in addition, no vaccines are available against these strains. This warrants efforts to propose a theoretical based multi-epitope vaccine construct to prevent pathogen infections . In this research, reverse vaccinology bioinformatics and immunoinformatics approaches were adopted for vaccine target identification and construction of a multi-epitope vaccine. In the first phase, a core proteome dataset of the targeted pathogen was obtained using the NCBI database and subjected to bacterial pan-genome analysis using bacterial pan-genome analysis (BPGA) to predict core protein sequences which were then used to find good vaccine target candidates. This identified two proteins, Hcp family type VI secretion system effector and superoxide dismutase family protein, as promising vaccine targets. Afterward using the IEDB database, different B-cell and T-cell epitopes were predicted. A set of four epitopes “KGSVNVQDRE, NTGKLTGTR, IIHSDSWNER, and KDGKPVPALK” were chosen for the development of a multi-epitope vaccine construct. A 183 amino acid long vaccine design was built along with “EAAAK” and “GPGPG” linkers and a cholera toxin B-subunit adjuvant. The designed vaccine model comprised immunodominant, non-toxic, non-allergenic, and physicochemical stable epitopes. The model vaccine was docked with MHC-I, MHC-II, and TLR-4 immune cell receptors using the Cluspro2.0 web server. The binding energy score of the vaccine was − 654.7 kcal/mol for MHC-I, − 738.4 kcal/mol for MHC-II, and − 695.0 kcal/mol for TLR-4. A molecular dynamic simulation was done using AMBER v20 package for dynamic behavior in nanoseconds. Additionally, MM-PBSA binding free energy analysis was done to test intermolecular binding interactions between docked molecules. The MM-GBSA net binding energy score was − 148.00 kcal/mol, − 118.00 kcal/mol, and − 127.00 kcal/mol for vaccine with TLR-4, MHC-I, and MHC-II, respectively. Overall, these in silico-based predictions indicated that the vaccine is highly promising in terms of developing protective immunity against P. penneri . However, additional experimental validation is required to unveil the real immune response to the designed vaccine.
Proteus penneri (P. penneri) is a bacillus-shaped, gram-negative, facultative anaerobe bacterium that is primarily an invasive pathogen and the etiological agent of several hospital-associated infections. P. penneri strains are naturally resistant to macrolides, amoxicillin, oxacillin, penicillin G, and cephalosporins; in addition, no vaccines are available against these strains. This warrants efforts to propose a theoretical based multi-epitope vaccine construct to prevent pathogen infections. In this research, reverse vaccinology bioinformatics and immunoinformatics approaches were adopted for vaccine target identification and construction of a multi-epitope vaccine. In the first phase, a core proteome dataset of the targeted pathogen was obtained using the NCBI database and subjected to bacterial pan-genome analysis using bacterial pan-genome analysis (BPGA) to predict core protein sequences which were then used to find good vaccine target candidates. This identified two proteins, Hcp family type VI secretion system effector and superoxide dismutase family protein, as promising vaccine targets. Afterward using the IEDB database, different B-cell and T-cell epitopes were predicted. A set of four epitopes "KGSVNVQDRE, NTGKLTGTR, IIHSDSWNER, and KDGKPVPALK" were chosen for the development of a multi-epitope vaccine construct. A 183 amino acid long vaccine design was built along with "EAAAK" and "GPGPG" linkers and a cholera toxin B-subunit adjuvant. The designed vaccine model comprised immunodominant, non-toxic, non-allergenic, and physicochemical stable epitopes. The model vaccine was docked with MHC-I, MHC-II, and TLR-4 immune cell receptors using the Cluspro2.0 web server. The binding energy score of the vaccine was - 654.7 kcal/mol for MHC-I, - 738.4 kcal/mol for MHC-II, and - 695.0 kcal/mol for TLR-4. A molecular dynamic simulation was done using AMBER v20 package for dynamic behavior in nanoseconds. Additionally, MM-PBSA binding free energy analysis was done to test intermolecular binding interactions between docked molecules. The MM-GBSA net binding energy score was - 148.00 kcal/mol, - 118.00 kcal/mol, and - 127.00 kcal/mol for vaccine with TLR-4, MHC-I, and MHC-II, respectively. Overall, these in silico-based predictions indicated that the vaccine is highly promising in terms of developing protective immunity against P. penneri. However, additional experimental validation is required to unveil the real immune response to the designed vaccine.Proteus penneri (P. penneri) is a bacillus-shaped, gram-negative, facultative anaerobe bacterium that is primarily an invasive pathogen and the etiological agent of several hospital-associated infections. P. penneri strains are naturally resistant to macrolides, amoxicillin, oxacillin, penicillin G, and cephalosporins; in addition, no vaccines are available against these strains. This warrants efforts to propose a theoretical based multi-epitope vaccine construct to prevent pathogen infections. In this research, reverse vaccinology bioinformatics and immunoinformatics approaches were adopted for vaccine target identification and construction of a multi-epitope vaccine. In the first phase, a core proteome dataset of the targeted pathogen was obtained using the NCBI database and subjected to bacterial pan-genome analysis using bacterial pan-genome analysis (BPGA) to predict core protein sequences which were then used to find good vaccine target candidates. This identified two proteins, Hcp family type VI secretion system effector and superoxide dismutase family protein, as promising vaccine targets. Afterward using the IEDB database, different B-cell and T-cell epitopes were predicted. A set of four epitopes "KGSVNVQDRE, NTGKLTGTR, IIHSDSWNER, and KDGKPVPALK" were chosen for the development of a multi-epitope vaccine construct. A 183 amino acid long vaccine design was built along with "EAAAK" and "GPGPG" linkers and a cholera toxin B-subunit adjuvant. The designed vaccine model comprised immunodominant, non-toxic, non-allergenic, and physicochemical stable epitopes. The model vaccine was docked with MHC-I, MHC-II, and TLR-4 immune cell receptors using the Cluspro2.0 web server. The binding energy score of the vaccine was - 654.7 kcal/mol for MHC-I, - 738.4 kcal/mol for MHC-II, and - 695.0 kcal/mol for TLR-4. A molecular dynamic simulation was done using AMBER v20 package for dynamic behavior in nanoseconds. Additionally, MM-PBSA binding free energy analysis was done to test intermolecular binding interactions between docked molecules. The MM-GBSA net binding energy score was - 148.00 kcal/mol, - 118.00 kcal/mol, and - 127.00 kcal/mol for vaccine with TLR-4, MHC-I, and MHC-II, respectively. Overall, these in silico-based predictions indicated that the vaccine is highly promising in terms of developing protective immunity against P. penneri. However, additional experimental validation is required to unveil the real immune response to the designed vaccine.
Author Hassan, Muhammad
Naz, Tahira
ul Haq, Mehboob
Sanami, Samira
Irfan, Muhammad
Rehman, Bushra
Waheed, Yasir
Khan, Saifullah
Almanaa, Taghreed N.
Muhammad, Riaz
Ahmad, Sajjad
Ullah, Asad
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  organization: Institute of Biotechnology and Microbiology, Bacha Khan University
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  organization: Institute of Biotechnology and Microbiology, Bacha Khan University
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  organization: Department of Health and Biological Sciences, Abasyn University, Department of Natural Sciences, Lebanese American University
BackLink https://www.ncbi.nlm.nih.gov/pubmed/37934390$$D View this record in MEDLINE/PubMed
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2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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Issue 12
Keywords Bacterial pan-genome analysis
Molecular dynamic simulation
Multi-epitope vaccine
Cholera toxin B-subunit
Proteus penneri
Language English
License 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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Snippet Proteus penneri ( P. penneri ) is a bacillus-shaped, gram-negative, facultative anaerobe bacterium that is primarily an invasive pathogen and the etiological...
Proteus penneri (P. penneri) is a bacillus-shaped, gram-negative, facultative anaerobe bacterium that is primarily an invasive pathogen and the etiological...
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SubjectTerms adjuvants
Amino acids
Amoxicillin
Antibiotics
B-lymphocytes
Bacteria
Binding energy
Biochemistry
Bioinformatics
Biological Techniques
Biotechnology
Cell Biology
Cephalosporins
Chemistry
Chemistry and Materials Science
Cholera
cholera toxin
Cholera toxin B subunit
computer simulation
Core protein
cross infection
data collection
energy
Epitopes
family
Free energy
Gene sequencing
Genomes
Genomic analysis
Gibbs free energy
Human Genetics
Immune response
Immune system
immunoinformatics
Internet
Lymphocytes B
Lymphocytes T
macrolides
Major histocompatibility complex
Molecular dynamics
Nosocomial infection
Original Paper
Oxacillin
Pathogens
Penicillin
Protein Science
Proteins
proteome
Proteomes
Proteus penneri
Strains (organisms)
Superoxide dismutase
T-lymphocytes
Thermodynamics
Toxins
type VI secretion system
vaccine development
Vaccines
Waterborne diseases
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Title An In Silico Multi-epitopes Vaccine Ensemble and Characterization Against Nosocomial Proteus penneri
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