Clin Exp Vaccine Res.  2015 Jan;4(1):99-106. 10.7774/cevr.2015.4.1.99.

In silico analysis for identifying potential vaccine candidates against Staphylococcus aureus

• Delfani S
• Imani Fooladi AA
• Mobarez AM
• Emaneini M
• Amani J
• Sedighian

• KMID: 2049113
• DOI: http://doi.org/10.7774/cevr.2015.4.1.99

Abstract

PURPOSE
Staphylococcus aureus is one of the most important causes of nosocomial and community-acquired infections. The increasing incidence of multiple antibiotic-resistant S. aureus strains and the emergence of vancomycin resistant S. aureus strains have placed renewed interest on alternative means of prevention and control of infection. S. aureus produces a variety of virulence factors, so a multi-subunit vaccine will be more successful for preventing S. aureus infections than a mono-subunit vaccine.
MATERIALS AND METHODS
We selected three important virulence factors of S. aureus, clumping factor A (ClfA), iron-regulated surface determinant (IsdB), and gamma hemolysin (Hlg) that are potential candidates for vaccine development. We designed synthetic genes encoding the clfA, isdB, and hlg and used bioinformatics tools to predict structure of the synthetic construct and its stabilities. VaxiJen analysis of the protein showed a high antigenicity. Linear and conformational B-cell epitopes were identified.
RESULTS
The proteins encoded by these genes were useful as vaccine candidates against S. aureus infections.
CONCLUSION
In silico tools are highly suited to study, design, and evaluate vaccine strategies.

Keyword

Computer simulation; Staphylococcus aureus; Vaccines

MeSH Terms

Community-Acquired Infections
Computational Biology
Computer Simulation*
Epitopes, B-Lymphocyte
Genes, Synthetic
Incidence
Staphylococcus aureus*
Vaccines
Vancomycin
Virulence Factors
Epitopes, B-Lymphocyte
Vaccines
Vancomycin
Virulence Factors

Figure

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  Fig. 1 Schematic representation of Staphylococcus aureus antigenic construct consists of clfA, isdB, and hlg genes bound together by appropriate linkers for expression in Escherichia coli.

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  Fig. 2 Analysis of wild type and optimized chimeric gene based on codon usage.

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  Fig. 3 (A) Prediction of RNA secondary structure of chimeric gene using mofld algorithm. (B) Predicted structure has no hairpin and pseudo knot at 5' site of mRNA.

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  Fig. 4 Graphical results for secondary structure prediction of chimeric protein. Purple, red, and blue colors indicate extended strand, coil, and helix, respectively.

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  Fig. 5 Modeled structure of chimeric protein by I-TASSER software. The three-dimensional modeled structure generated by I-TASSER software showed a protein with three main domains linked together with linkers.

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  Fig. 6 Validation of protein structure using Ramachandran plot. The Ramachandran plot shows that 75.3% of amino acid residues from modeled structure were incorporated in the favored regions of the plot. Fourteen point six percentages of the residues were in allowed regions of the plot and 10.1% of residue in outlier region.

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