Impact of polymorphisms in blaZ, blaR1 and blaI genes and their relationship with β-lactam resistance in S. aureus strains isolated from bovine mastitis

Abstract

There is not a consensus between the presence of the genotypic resistance marker gene and the phenotypic resistance to β-lactams in Staphylococcus aureus, which means, positive S. aureus blaZ isolates demonstrating sensitivity to β-lactams. The present study aimed to characterize the blaZ, blaR1 and blaI genes, identify and evaluate single nucleotide polymorphisms (SNPs) and their relationship with β-lactam resistance in samples of Staphylococcus aureus obtained from cases of bovine mastitis. Five isolates (two resistant and three sensitive to oxacillin) of Staphylococcus aureus with detected production of beta-lactamase, previously evaluated as containing the blaZ gene and negative for the mecA and mecC genes, had the bla operon completely sequenced. Impacts on the protein sequence due to the detected polymorphisms were evaluated by modeling the proteins encoded by the blaZ, blaR1 and blaI genes using a three-dimensional model structure obtained from the Protein Data Bank (PDB) database. Fifteen SNPs were detected in the blaZ gene, 30 in the blaR1 gene and three in the blaI gene. These SNPs caused alterations in amino acid sites. Deleterious mutations were detected in the blaZ gene (E146G, P218S, Y221C) and the blaR1 gene (K481E). Molecular docking analysis revealed that polymorphisms in the blaZ gene may explain the phenotypic sensitivity in isolates that contain the resistance marker gene. Although sensitive and resistant isolates encode beta-lactamase, these proteins are functionally altered due to a change in the binding site with the antibiotic.