Resistome Profiling of a Large Collection of Staphylococcus aureus Isolates Uncovers Frameshift-Silenced mupA Gene

Martyna Kasela1, Katarzyna Suśniak1, Mateusz Ossowski2

  • 1Department of Pharmaceutical Microbiology, Medical University of Lublin, 1 Chodźki St., 20-093 Lublin, Poland.

Insights

Silent Staphylococcus aureus resistance genes, particularly mupirocin resistance (mupA), are crucial for surveillance. Frameshift mutations in mupA prevent resistance, highlighting silent genes as targets against emerging threats.

Area of Science:

  • Microbiology
  • Genetics
  • Infectious Diseases

Background:

  • Staphylococcus aureus is a high-priority pathogen causing skin and soft tissue infections (SSTIs).
  • Frequent antimicrobial resistance necessitates accurate diagnostics for effective therapy.
  • Understanding resistance mechanisms, including gene silencing, is critical.

Purpose of the Study:

  • Compare phenotypic and genotypic resistance in S. aureus from nasal carriers and SSTIs.
  • Investigate gene-silencing mechanisms, focusing on the mupA gene.
  • Elucidate the role of mutations in silent resistance genes.

Main Methods:

  • Phenotypic and genotypic resistance profiling of 355 S. aureus isolates.
  • Sequencing of the silenced mupA gene.
  • Reverse transcription quantitative PCR (RT-qPCR) to assess gene expression.

Main Results:

  • SSTI isolates showed higher resistance to erythromycin, gentamicin, and mupirocin.
  • Higher prevalence of multidrug-resistant strains, ermC, and tetM genes in SSTI isolates.
  • Frameshift mutations (e.g., c.372 delA) in silent mupA were identified, leading to premature truncation and preventing resistance.

Conclusions:

  • Silent resistance genes represent key targets for S. aureus surveillance.
  • Frameshift mutations in mupA suggest a mechanism preventing functional resistance.
  • Findings aid in combating emerging antimicrobial resistance threats.

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