In silico epitope identification of unique multidrug resistance proteins from Salmonella Typhi for vaccine development

Jebastin, Thomas; Narayanan, Shridhar

doi:10.1016/j.compbiolchem.2018.11.020

Cited by 17 publications

(4 citation statements)

References 55 publications

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“…30 Epitopes from multidrug-resistant Salmonella have been identi ed from TolC protein previously. 31 The outer membrane proteins such as TolC protein being unique to Gram-negative bacteria could serve as a potential vaccine candidate. 32 The TolC protein has been recently shown to be protective against V. harveyi infection.…”

Section: Discussionmentioning

confidence: 99%

Identification and Computational Validation of TolC Derived B- and T- Cell Epitopes for the Development of Pan-Rickettsial Vaccine

Sankar

Subramanian

Venkatesan³

2022

Preprint

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Introduction: Rickettsia is vector-borne causing Rickettsial infections with high mortality. Currently, no vaccines are available for the prevention of rickettsioses. The study aims to identify B- and T- cell epitopes to peptides derived from TolC protein of rickettsial group of pathogens. Immunogenic linear B-cell epitopes and MHC class I and II T-cell epitopes predicted from the consensus sequences of TolC protein for each rickettsial species. The putative antigenic epitopes may trigger an effective immune response and prove to be a novel vaccine that protects against all rickettsial infections. Methods: MHC class-I binding T-cell epitopes were predicted along with TAP binding efficiency and proteasomal cleavage sites. Molecular docking study was carried out to investigate the binding affinity between the MHC-I protein molecules with the peptides. The MHC-peptide complex with the highest RMSD score was further used for molecular dynamic simulation study.Results: Three B-cell candidate peptide epitopes were selected, of which epitope IYPEGGAQYSRIRSAKNQTRNSA/VVQ is conserved across both typhus group and spotted fever group of rickettsial species was considered best suitable for candidate vaccine. The peptide epitope KLYEAKITR had a good RMSD score as well as promiscuous binding to 28 different HLA allele supertypes and was considered suitable for the development of subunit peptide vaccine. Conclusion: The B- and T- cell candidate peptide epitopes identified in our study would elicit B- and T-cell immune responses respectively and serve as a novel candidate peptide vaccine.

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Section: Discussionmentioning

confidence: 99%

Identification and Computational Validation of TolC Derived B- and T- Cell Epitopes for the Development of Pan-Rickettsial Vaccine

Sankar

Subramanian

Venkatesan³

2022

Preprint

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“…Quiroz et al, as well as Mendiola et al, reported the inhibition of shikimate dehydrogenase as a potential drug target to inhibit E. coli and MRSA, whereas other studies have reported it inhibiting the pantothenate synthetase against MTB to minimize the prolonged TB treatment [44]. However, Jebastin et al and Kazi et al, described the role of outer membrane proteins such as Emrs, OMPs, and Mdts as a potent vaccine candidate for chimeric vaccine designing against Shigella flexneri [56] as well as Salmonella Typhi [57]. Similarly, the identified Mdtc protein can be considered for future vaccine design against S. Typhi.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Therapeutic Target against XDR Salmonella Typhi H58 Using Genomics Driven Approach Followed Up by Natural Products Virtual Screening

et al. 2021

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Typhoid fever is caused by a pathogenic, rod-shaped, flagellated, and Gram-negative bacterium known as Salmonella Typhi. It features a polysaccharide capsule that acts as a virulence factor and deceives the host immune system by protecting phagocytosis. Typhoid fever remains a major health concern in low and middle-income countries, with an estimated death rate of ~200,000 per annum. However, the situation is exacerbated by the emergence of the extensively drug-resistant (XDR) strain designated as H58 of S. Typhi. The emergence of the XDR strain is alarming, and it poses serious threats to public health due to the failure of the current therapeutic regimen. A relatively newer computational method called subtractive genomics analyses has been widely applied to discover novel and new drug targets against pathogens, particularly drug-resistant ones. The method involves the gradual reduction of the complete proteome of the pathogen, leading to few potential and novel drug targets. Thus, in the current study, a subtractive genomics approach was applied against the Salmonella XDR strain to identify potential drug targets. The current study predicted four prioritized proteins (i.e., Colanic acid biosynthesis acetyltransferase wcaB, Shikimate dehydrogenase aroE, multidrug efflux RND transporter permease subunit MdtC, and pantothenate synthetase panC) as potential drug targets. Though few of the prioritized proteins are treated in the literature as the established drug targets against other pathogenic bacteria, these drug targets are identified here for the first time against S. Typhi (i.e., S. Typhi XDR). The current study aimed at drawing attention to new drug targets against S. Typhi that remain largely unexplored. One of the prioritized drug targets, i.e., Colanic acid biosynthesis acetyltransferase, was predicted as a unique, new drug target against S. Typhi XDR. Therefore, the Colanic acid was further explored using structure-based techniques. Additionally, ~1000 natural compounds were docked with Colanic acid biosynthesis acetyltransferase, resulting in the prediction of seven compounds as potential lead candidates against the S. Typhi XDR strain. The ADMET properties and binding energies via the docking program of these seven compounds characterized them as novel drug candidates. They may potentially be used for the development of future drugs in the treatment of Typhoid fever.

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“…Molecular weight analysis is considered crucial in terms of proteins puri cation [26]. Ideally, proteins with a molecular weight of less than 110 kDa are regarded as effective vaccine targets [34,39,40]. VaxiJen 2.0 was used to determine antigenicity of proteins, with organism set to bacteria and a threshold of > 0.6 [41].…”

Section: Prioritization Of Potential Candidatesmentioning

confidence: 99%

An In-depth Genomic Investigation to Design a Multi-Epitope Based Vaccine against Brucellosis

Hameed

Mohammed

Jassim

et al. 2023

Preprint

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Brucella melitensis is a gram-negative coccobacillus that causes brucellosis in humans when they come into contact with infected animal meat or consumed raw milk. The lack of effective treatment and increasing antibiotic resistant patterns shown by B. melitensis warrant the search for novel therapeutic targets. In this study, comprehensive bioinformatics, reverse vaccinology, and biophysics techniques were employed to design a novel multi-epitopes-based vaccine (MEBV) against B. melitensis. Pan-genomics, subtractive proteomics and immunoinformatic studies revealed three core proteins: Flagellar hook protein (FlgE), TonB-dependent receptor, and Porin family protein as promising vaccine targets. The proteins have exposed topology, are antigenic, and are adhesin. Furthermore, B and T cell epitopes were predicted from these target proteins. Highly antigenic, immunogenic, and non-allergenic epitopes were shortlisted and used in the MEBV vaccine design. The designed MEBV also showed stable docked conformation with different immune receptors such as MHC-I, MHC-II, and TLR-4. It was found that all three systems showed robust binding energies with net binding energy < -300 kcal/mol. The van der Waals and electrostatic energies were the dominating energies and were found to be the stabilizing factors of complexes. The designed vaccine contains antigenic epitopes that were filtered using stringent criteria. The vaccine was also predicted to generate promising immunological responses and thus could be an attractive candidate for evaluation in experimental studies.

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In silico epitope identification of unique multidrug resistance proteins from Salmonella Typhi for vaccine development

Cited by 17 publications

References 55 publications

Identification and Computational Validation of TolC Derived B- and T- Cell Epitopes for the Development of Pan-Rickettsial Vaccine

Identification and Computational Validation of TolC Derived B- and T- Cell Epitopes for the Development of Pan-Rickettsial Vaccine

Identification of a Novel Therapeutic Target against XDR Salmonella Typhi H58 Using Genomics Driven Approach Followed Up by Natural Products Virtual Screening

An In-depth Genomic Investigation to Design a Multi-Epitope Based Vaccine against Brucellosis

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