Subtractive proteomic analysis for identification of potential drug targets and vaccine candidates against Burkholderia pseudomallei K96243

Khan, Md Abu Sayem; Miah, Md Ibrahim; Rahman, Sabita Rezwana

doi:10.1016/j.imu.2022.101127

Cited by 3 publications

(3 citation statements)

References 62 publications

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“…Finally, two enzymes, dihydroneopterin aldolase, and phosphoribosyl transferase were predicted as novel drug targets. Also, the research identified the antibiotics cefiderocol and tetracycline show the best affinity towards the selected target (Khan et al, 2022). Recently, Walter et al studied the molecular mechanism and effect of UTP binding to the UMP kinase enzyme of Mycobacterium tuberculosis bacteria by using X-ray crystallography and cryo-electron microscopy.…”

Section: Structure Prediction Of the Uridylate Kinasementioning

confidence: 99%

In-silico Prediction of Drug Target, Molecular Modeling, and Docking Study of Potential Inhibitors against Burkholderia pseudomallei

Satpathy¹

2023

J Biochem Technol

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The infection of the Burkholderia pseudomallei causes the disease melioidosis. for which the treatment method takes longer time, and sometimes it is difficult to completely eradicate the bacteria from the body. Moreover, its antibiotic resistance in nature created great concern in recent times. Hence, there is an urgent requirement to identify new drug molecules that can improve the current process of treatments and reduce the risk to people. This study analyzed the pyrimidine metabolic pathways of Burkholderia pseudomallei strain K96243, and UMP (Uridine monophosphate/Uridylate) kinase enzyme was selected as the drug target. After structure prediction by the AlphaFold server, the validation of the structure was performed by using Procheck, Verify3D, and Errat tool. Further, six probable inhibitor molecules were selected from the PubChem database, including the natural inhibitor of the enzyme, Uridine triphosphate (UTP). The molecular docking study predicted that the UTP (CID 6133) had the highest docking score, followed by another compound PubChem (Compound ID) CID 284262. Then, Toxicity and ADMET properties were computed and analyzed. Further, a 5 nanosecond molecular dynamics simulation of the complex of UMP-Kinase and CID 284262 was performed by using the Gromacs 5.1.1 software to analyze the stability of the best complex. It was predicted that the CID 284262 might be considered a suitable inhibitor of the enzyme.

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Section: Structure Prediction Of the Uridylate Kinasementioning

confidence: 99%

In-silico Prediction of Drug Target, Molecular Modeling, and Docking Study of Potential Inhibitors against Burkholderia pseudomallei

Satpathy¹

2023

J Biochem Technol

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“…B. pseudomallei utilizes several virulence factors like quorum sensing, secretion system, capsular polysaccharide, flagella, etc., along with siderophores and different enzymes like protease, lipase, catalase, superoxide dismutase, etc., for disease colonization, persistence, and latency [6,7]. Being a facultative intracellular pathogen, the life cycle of B. pseudomallei includes adhesion, penetration into host cells, phagosome escape, cytosolic replication, and cell-to-cell dissemination [8].…”

Section: Introductionmentioning

confidence: 99%

Designing a novel Scaffold-Based Multi-Epitope Vaccine to Combat Melioidosis Caused by Burkholderia pseudomallei: AnIn-silicoand Immunoinformatics approach

Rahman,

Das,

Das

et al. 2024

Preprint

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Burkholderia pseudomallei, the gram-negative bacteria causing melioidosis, is becoming a serious threat to healthcare settings. In recent years,B. pseudomalleihas been identified as an emerging and significant etiological agent responsible for localized pyogenic infections primarily observed in India and South Asia. At present, no vaccine against melioidosis is available in the treatment system. This study has undertaken anin-silicoreverse vaccinology approach to design a novel multi-epitope vaccine for treatingB. pseudomallei-mediated infections. B-cell and T-cell epitopes have been predicted and stitched to develop a multi-epitope vaccine. The predicted vaccine is found to be non-toxic, non-allergic, and immunogenic in nature. Immune simulation results indicate that the designed vaccine can generate an immune response resembling a real-life scenario. The 610 amino-acid long vaccine construct has been codon-optimized and could be cloned in the E. coli K12 system. These findings from this immunoinformatics study offer a foundation for developing a tailored, safe, and potent vaccine targetingB. pseudomallei.

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“…Immunopeptidomics is a field of study that examines the collections of all peptides connected to human leukocyte antigen (HLA) molecules, and it is frequently fueled by mass spectrometry (MS) technologies. In recent years, several in-silico approaches have been used to predict and design multi-epitope peptides capable of bounding to major histocompatibility complexes (MHC) (Paul et al, 2021;Moradi et al, 2022;Oladipo et al, 2022;Khan et al, 2022;Ghulam et al, 2022;Islam et al, 2022). This study sought to develop a B-cell multi-epitope peptide for the diagnosis of MRSA infection from the blood of individuals with MRSA blood stream infection using an immunoinformatics approach, which may aid in immune response and improve serodiagnosis accuracy while speeding up diagnosis, particularly for those residing in developing and endemic areas.…”

Section: Introductionmentioning

confidence: 99%

Immunoinformatics design of B-cell multi-epitope peptide for the diagnosis of Methicillin Resistant Staphylococcus aureus (MRSA) infection

Olatunde,

Owolabi,

Ayinde

et al. 2023

F1000Res

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Background: Methicillin (oxacillin)-resistant Staphylococcus aureus (MRSA) remains a significant clinical and epidemiological pathogen in hospital settings and in the community world-wide. The resistance to methicillin in Staphylococcus aureus is mediated by the mecA gene, which encodes penicillin-binding protein 2a (PBP2A). Rapid patient screening for MRSA is essential for infection control procedures in order to possibly enhance the outcomes of infected patients. In this study, we utilized PBP2A to predict and create a novel synthetic protein with multiple immunodominant B cell epitopes for rapid diagnosis of MRSA using an in-silico approach. Methods: Seven putative PBP2A peptides were used to analyze the protein’s primary, secondary, and tertiary structures (BepiPred). The B cell construct was then evaluated using I-TASSER server, and physicochemical properties, and homology modeling of the 3 D structure of the protein were obtained. Results: In silico analyses revealed regions with high immunogenicity. Altogether, 19 consented epitopes were selected for the in-silico succession; three consented epitopes from ALJ10988.1, three from ORN56903.1, three from AFJ06714.1, one from AEO00772.1, three from WP_000721309.1, three from WP_057521704.1, and three from WP_063851348.1. The constructs have an average length of 503 amino acids, molecular weight of 55,151.78, instability index of 41.44, theoretical PI of 9.28 and a C score −1.50. In addition, the parameters that were examined indicated the newly multi-epitope construct could potentially serve as a theoretical framework for the development of a MRSA diagnostic kit. Conclusions: Overall, we have developed an antigen-based multi-epitope peptide for the rapid and accurate diagnosis of MRSA infection through an in-silico approach, acceptable in terms of antigenicity, physicochemical properties, structural stability and strong immunogenicity.

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Subtractive proteomic analysis for identification of potential drug targets and vaccine candidates against Burkholderia pseudomallei K96243

Cited by 3 publications

References 62 publications

In-silico Prediction of Drug Target, Molecular Modeling, and Docking Study of Potential Inhibitors against Burkholderia pseudomallei

In-silico Prediction of Drug Target, Molecular Modeling, and Docking Study of Potential Inhibitors against Burkholderia pseudomallei

Designing a novel Scaffold-Based Multi-Epitope Vaccine to Combat Melioidosis Caused by Burkholderia pseudomallei: AnIn-silicoand Immunoinformatics approach

Immunoinformatics design of B-cell multi-epitope peptide for the diagnosis of Methicillin Resistant Staphylococcus aureus (MRSA) infection

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