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Parallel Evolution of Linezolid Resistant Staphylococcus aureus in Patients with Cystic Fibrosis

Nicholas J Pitcher1, Andries Feder2, Nicholas Bolden3

  • 1Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242.

Biorxiv : the Preprint Server for Biology
|May 19, 2023
PubMed
Abstract

Insights

Linezolid resistance in Staphylococcus aureus emerged in 4 of 111 cystic fibrosis patients. Multiple genetic mechanisms, including mutations and hypermutability, contributed to this resistance, primarily in MRSA backgrounds.

Area of Science:

  • Microbiology
  • Genetics
  • Infectious Diseases

Background:

  • Linezolid is a critical antibiotic for treating serious Staphylococcus aureus infections.
  • Emergence of linezolid resistance, though rare, is a growing concern, particularly with repeated antibiotic exposure.
  • Previous reports indicated widespread linezolid use in cystic fibrosis (CF) patients.

Approach:

  • Investigated the incidence and molecular mechanisms of linezolid resistance in Staphylococcus aureus from cystic fibrosis patients.
  • Analyzed patient isolates using broth microdilution for susceptibility testing.
  • Employed whole genome sequencing for phylogenetic analysis and identification of resistance-conferring mutations or genes.

Key Points:

  • Linezolid resistance developed in 4 out of 111 cystic fibrosis patients treated between 2008 and 2018.
  • Identified multiple genetic pathways leading to linezolid resistance, including specific mutations in 23S rRNA and the presence of hypermutating phenotypes.
  • All identified resistant strains originated from ST5 or ST105 Methicillin-Resistant Staphylococcus aureus (MRSA) backgrounds.

Conclusions:

  • Linezolid resistance in Staphylococcus aureus can arise through diverse genetic mechanisms.
  • Hypermutator phenotypes may accelerate the evolution of linezolid resistance.
  • Observed transient nature of linezolid resistance suggests a potential fitness cost to resistant strains.

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