Clinical isolates of Staphylococcus aureus with ribosomal mutations conferring resistance to macrolides

Area of Science:

• Microbiology
• Genetics
• Molecular Biology

Background:

• Staphylococcus aureus is a common pathogen, particularly in cystic fibrosis (CF) patients.
• Macrolide antibiotics like azithromycin are used to treat chronic S. aureus infections in CF.
• Antibiotic resistance is a growing concern in managing CF pulmonary exacerbations.

Purpose of the Study:

• To investigate the mechanism of azithromycin and erythromycin cross-resistance in Staphylococcus aureus strains isolated from CF patients.
• To identify specific genetic mutations responsible for the observed resistance phenotype.

Main Methods:

• Isolation and characterization of Staphylococcus aureus strains from CF patients post-azithromycin treatment.
• Phenotypic antibiotic susceptibility testing for azithromycin and erythromycin.
• Genotypic analysis, including PCR and sequencing, to detect erm and msr(A) genes and mutations in ribosomal RNA (rrl) and ribosomal protein (rplV) genes.

Main Results:

• Six S. aureus strains exhibited cross-resistance to azithromycin and erythromycin.
• No erm or msr(A) resistance genes were detected in any of the isolates.
• All resistant strains harbored A2058G/U or A2059G mutations in the 23S rRNA (rrl) genes.
• A majority of rRNA copies carried these mutations.
• One strain also presented a mutation in the rplV gene.

Conclusions:

• Azithromycin and erythromycin cross-resistance in these CF-associated S. aureus strains is mediated by specific mutations in ribosomal RNA genes (A2058G/U or A2059G).
• The absence of common macrolide resistance genes suggests alternative resistance mechanisms are prevalent in this clinical context.
• The findings highlight the importance of understanding novel resistance mechanisms to guide effective antibiotic therapy in cystic fibrosis.