Genomic alterations involved in fluoroquinolone resistance development in Staphylococcus aureus

Thuc Quyen Huynh1,2,3, Van Nhi Tran1,3, Van Chi Thai1,3

  • 1School of Biotechnology, International University, Ho Chi Minh City, Vietnam.

Plos One
|July 26, 2023
PubMed
Abstract

Insights

Fluoroquinolone (FQ) resistance in Staphylococcus aureus emerges due to target mutations and increased efflux pump activity. This study investigated the mechanisms behind multidrug-resistant (MDR) S. aureus development under FQ exposure.

Area of Science:

  • Microbiology
  • Genetics
  • Pharmacology

Background:

  • Fluoroquinolones (FQ) are critical antibiotics, but their efficacy is threatened by rapidly emerging resistance.
  • Staphylococcus aureus (S. aureus) can develop multidrug resistance (MDR), posing a significant clinical challenge.

Purpose of the Study:

  • To investigate the genomic and molecular mechanisms driving the emergence of MDR S. aureus strains following exposure to fluoroquinolones.
  • To identify specific mutations and gene expression changes associated with FQ resistance in S. aureus.

Main Methods:

  • Serial sub-minimum inhibitory concentration (sub-MIC) exposure of S. aureus ATCC 29213 to ciprofloxacin, ofloxacin, or levofloxacin.
  • Whole genome sequencing (WGS) and target sequencing to identify genomic alterations.
  • RT-qPCR to quantify the expression levels of genes involved in FQ resistance, efflux pumps, and alternative sigma factors.

Main Results:

  • Significant and irreversible increases in minimum inhibitory concentrations (MICs) for FQs were observed in exposed S. aureus strains.
  • WGS revealed multiple mutations in FQ-exposed strains, including alterations in GrlA (R570H), SACOL0573, and rimI.
  • Overexpression of genes related to efflux pumps (norA, norB, norC, mgrA) and alternative sigma factors (sigB, sigS) was detected in FQ-resistant strains.

Conclusions:

  • The emergence of MDR S. aureus under FQ pressure is strongly linked to mutations within FQ target sequences.
  • Upregulation of efflux pump systems and their regulators plays a crucial role in the development of fluoroquinolone resistance in S. aureus.

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