Delineating Novel Therapeutic Drug and Vaccine Targets for Staphylococcus cornubiensis NW1T Through Computational Analysis

Abstract

Staphylococcal multidrug resistance is an emerging future threat. Among staphylococci species, Staphylococcus intermedius group (SIG) comprises of coagulase-positive four staphylococci isolated from veterinary wounds and post-operative infections in humans and animals. Staphylococcus cornubiensis has been reported as a new member of this group and is associated with infections in a wide range of wild and domesticated animals as well as in humans. Cases of the antibiotic resistance in different members of the SIG are reported indicating its future threat for antibiotic therapy. The objective of this study was to determine the unique potential drug and vaccine targets for infectious S. cornubiensis NW1T. Genome-wide subtractive proteomic approach accompanied by immunoinformatics analysis was performed on the newly reported genome of S. cornubiensis NW1T. Applying a stringent comparative proteomic analyses, 35 proteins were identified as novel druggable targets based on their function in pathogen specific metabolic pathways as well as their druggablity potential. Using antigenicity and epitope prediction methods, the possible B and T-cells antigenic peptides of these pathogen-specific essential proteins were determined. As a result, six proteins were prioritized as potential vaccine candidates that fulfilled the basic criteria of effective vaccine targets. During analyses, candidate proteins of S. cornubiensis were found to carry T-cell and B-cell epitopes and predicted to interact with both class I and II MHC molecules at significantly lower IC50 values. Moreover, a leading antigenic peptide “LVDTLNAAG” from penicillin binding protein of this pathogenic bacteria was found to interact with multiple MHC alleles of class I and II with IC50 value of < 100 nM. Molecular docking showed favorable interactions between this lead antigenic peptide with human HLA-C*05:01 cell surface receptor. This peptide is predicted as a promising epitope capable of triggering the immune response against pathogenic S. cornubiensis NW1T. The candidate proteins and epitopes determined in this study may be promising novel drug and vaccine targets against infection-causing S. cornubiensis.

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Acknowledgements

The authors are thankful to Mr. Hizbullah for his technical help during the research work. We are also thankful to Bahauddin Zakariya University, Multan for providing infrastructure to conduct this research work.

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Supplementary Table S1.

The S. cornubiensis human-host non-homologous essential proteins involved in 37 unique metabolic pathways prioritized as drug targets. (DOCX 27 kb)

Supplementary Table S2.

Major MHC-I binding epitopes predicted for putative S. cornubiensis vaccine targets. (XLSX 381 kb)

Supplementary Table S3.

Predicted MHC-II binding epitopes for potential vaccine targets. (XLSX 119 kb)

Supplementary Table S4.

The top-ranked MHC-I/II peptides as vaccine targets. (DOCX 16 kb)

Supplementary Table S5.

Predicted linear B-cell epitopes for putative S. cornubiensis vaccine targets. (DOCX 13 kb)

Supplementary Fig. 1.

The figure shows the conformational B-cell epitopes for potential vaccine target i.e. penicillin-binding protein of S. cornubiensis predicted by Ellipro server of IEDB. (JPG 367 kb)

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Shah, M., Jaan, S., Fatima, B. et al. Delineating Novel Therapeutic Drug and Vaccine Targets for Staphylococcus cornubiensis NW1T Through Computational Analysis. Int J Pept Res Ther 27, 181–195 (2021). https://doi.org/10.1007/s10989-020-10076-w

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Keywords

  • Subtractive genomics
  • Multi-drug resistance
  • Staphylococcus cornubiensis
  • Epitopes
  • Staphylococcus intermedius group