Work

Genomic alterations involved in fluoroquinolone resistance development in Staphylococcus aureus

Year: 2023

Type: article

Abstract: Aim Fluoroquinolone (FQ) is a potent antibiotic class. However, resistance to this class emerges quickly which hinders its application. In this study, mechanisms leading to the emergence of multidrug-resistant (MDR) Staphylococcus aureus ( S . aureus ) strains under FQ exposure were investigated. Methodology S . aureus ATCC 29213 was serially exposed to ciprofloxacin (CIP), ofloxacin (OFL), or levofloxacin (LEV) at sub-minimum inhibitory concentrations (sub-MICs) for 12 days to obtain S . aureus -1 strains and antibiotic-free cultured for another 10 days to obtain S . aureus -2 strains. The whole genome (WGS) and target sequencing were applied to analyze genomic alterations; and RT-qPCR was used to access the expressions of efflux-related genes, alternative sigma factors, and genes involved in FQ resistance. Results A strong and irreversible increase of MICs was observed in all applied FQs (32 to 128 times) in all S . aureus -1 and remained 16 to 32 times in all S . aureus -2. WGS indicated 10 noticeable mutations occurring in all FQ-exposed S . aureus including 2 insdel mutations in SACOL0573 and rimI ; a synonymous mutation in hslO ; and 7 missense mutations located in an untranslated region. GrlA, was found mutated (R570H) in all S . aureus -1 and -2. Genes encoding for efflux pumps and their regulator ( norA , norB , norC , and mgrA ); alternative sigma factors ( sigB and sigS ); acetyltransferase ( rimI ); methicillin resistance ( fmtB ); and hypothetical protein BJI72_0645 were overexpressed in FQ-exposed strains. Conclusion The emergence of MDR S . aureus was associated with the mutations in the FQ-target sequences and the overexpression of efflux pump systems and their regulators.

Source: PLoS ONE

DOI: 10.1371/journal.pone.0287973