Background and Objective: Staphylococcus aureus (S. aureus) is a gram-positive bacterium and one of the major nosocomial pathogen. It has the ability to acquire resistance against almost all available classes of antibiotics; Methicillin-Resistant S. aureus (MRSA) is a well-known antibiotic resistance. S. aureus is a globally distributed pathogen that need in-depth epidemiological and genomic level investigation for proper treatment and prevention. Methods: To explore the genomic epidemiology of S. aureus in-silico Multi Locus Sequence Typing (MLST) was carried out for 355 complete genomes. Diversity within the species was investigated through pan-genome analysis and subtractive genomic approach was employed for identification of core immunogenic targets. Results: Epidemiological study identified 62 different sequence types (STs) of S. aureus distributed worldwide, in which ST-8, ST-5, ST-398, ST-239, and ST-30 are the most dominant STs comprising more than 50% of the isolates. The pan-genome of S. aureus is still open with 7,199 genes and there is a major contribution (80%) of MRSA strains in the S. aureus species pangenome. The core genome (2,025 genes) of S. aureus is almost stable (comprises of 72% of S. aureus genome size) while accessory and unique genes (28% of S. aureus genome size) are gradually increasing. Screening of 2,025 core genes identified putative vaccine candidates. The best scoring and dominant B-cell and T-cell epitopes were predicted out of the selected potential vaccine candidate proteins with the help of a multi-step screening procedure. Conclusion: We believe that the current study will provide insight into the genetic epidemiology and diversity of S. aureus and the predicted epitopes against the pathogen can be tested further for its immunological responses within the host and may provide both humoral and cellular immunity against the disease.

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