Silent mupirocin resistance in methicillin-resistant Staphylococcus aureus

Staphylococcus aureus, including methicillin-resistant strains (MRSA), is a bacterium responsible for multiple types of human infections. The discrepancy between phenotypic and genotypic resistance is called silencing of antibiotic resistance by mutation (SARM), while the genes are called silent or cryptic. The presence of SARM bacteria carries a risk of implementing an ineffective antimicrobial drug in therapy, as the gene would not be activated until therapy. This study aimed to determine the frequency of SARM and its genetic mechanisms. The virulence and sequence type of the SARM strains were also characterized.

In total, 334 S. aureus strains were investigated for phenotypic resistance to cefoxitin, erythromycin, tetracycline, gentamycin, and mupirocin. PCR was used to screen for the presence of corresponding antibiotic-resistance genes. SARM isolates were further characterized by the detection of genes encoding toxins, adhesins, types of SCCmec cassette, and genotyping with MLST. Silenced genes were sequenced to determine the genetic defect and its consequences for protein translation.

The analysis showed the presence of SARM in 0.6% of S. aureus strains (2/334). In both cases, they were strains harbouring the mupA gene (resistance to mupirocin). Sequencing showed the presence of a deletion, resulting in the incorrect translation of the nucleotide into an amino acid sequence, shortening the amino acid chain and inhibiting the synthesis of the protein responsible for mupirocin resistance.

Mupirocin is an antibiotic applied in the treatment of staphylococcal infection of the skin, including the eradication (the removal of a microorganism from the body) of S. aureus from the nasal cavity. Despite the fact that the analysis showed a low share of SARM (<1%), there is still a risk of antimicrobial therapy failure and reinfection. Further studies should also focus on determining factors that increase the probability of activation of silent genes responsible for resistance to mupirocin.