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Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) is a significant clinical problem, the principal resistance determinant of which is the mecA gene. This paper uses extensive bioinformatics resources to determine Methicillin resistance gene A (mecA) on the various levels such as sequence analysis, phylogenetic reconstruction, prediction of protein structure and molecular docking. Methods We identified and used National Center for Biotechnology Information, GenBank, Clustal Omega, MEGA X, SWISS-MODEL, and AutoDock Vina to retrieve and analyze twenty-five mecA sequences in various strains of MRSA. Results Findings showed a high level of sequence conservation (97.2–99.8% identity) to the presence of absolutely conserved catalytic residues (Ser403, Lys406, Thr600). Phylogenetic studies confirmed that mecA was spread by horizontal gene transfer using Staphylococcal Cassette Chromosome mec (SCCmec) traveling elements. PBP2a was shown to have a constricted active site that was identified through three-dimensional modeling, which causes low beta-lactam affinity. Phenotypic resistance was described by the use of molecular docking indicating a weak binding of methicillin to PBP2a (-4.2 kcal/mol) in comparison to the native Penicillin-binding protein 2 (PBP2) (-7.5 kcal/mol). The functional analysis has determined that there are three domains and new motifs of PBP2a. Comparative analysis of SCCmec showed the presence of fourteen types (I-XIV) having different sizes and resistance genes. Conclusions These results offer a molecular understanding of resistance to methicillin and can be used as a guide to develop novel anti-MRSA drugs with potential therapeutic targets.
Dawood et al. (Thu,) studied this question.