Genomic alterations involved in fluoroquinolone resistance development in Staphylococcus aureus.
PLoS One
; 18(7): e0287973, 2023.
Article
em En
| MEDLINE
| ID: mdl-37494330
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções Estafilocócicas
/
Staphylococcus aureus
Limite:
Humans
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Vietnã