Ciprofloxacin enhances the biofilm formation of Staphylococcus aureus via an agrC -dependent mechanism

readily forms biofilms on host tissues and medical devices, enabling its persistence in chronic infections and resistance to antibiotic therapy. The accessory gene regulator (Agr) quorum sensing system plays a key role in regulating biofilm formation. This study reveals the widely used fluoroquinolo...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in microbiology 2023-12, Vol.14, p.1328947-1328947
Main Authors: Luo, Zhao-Xia, Li, Yuting, Liu, Mei-Fang, Zhao, Rui
Format: Article
Language:English
Subjects:
Agr
agrC
biofilm
ciprofloxacin
Microbiology
Staphylococcus aureus
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:readily forms biofilms on host tissues and medical devices, enabling its persistence in chronic infections and resistance to antibiotic therapy. The accessory gene regulator (Agr) quorum sensing system plays a key role in regulating biofilm formation. This study reveals the widely used fluoroquinolone antibiotic, ciprofloxacin, strongly stimulates biofilm formation in methicillin-resistant , methicillin-sensitive , and clinical isolates with diverse genetic backgrounds. Crystal violet staining indicated that ciprofloxacin induced a remarkable 12.46- to 15.19-fold increase in biofilm biomass. Confocal laser scanning microscopy revealed that ciprofloxacin induced denser biofilms. Phenotypic assays suggest that ciprofloxacin may enhance polysaccharide intercellular adhesin production, inhibit autolysis, and reduce proteolysis during the biofilm development, thus promoting initial adhesion and enhancing biofilm stability. Mechanistically, ciprofloxacin significantly alters the expression of various biofilm-related genes ( , , , , , ) and regulators ( , ). Gene knockout experiments revealed that deletion of , rather than , abolishes the ciprofloxacin-induced enhancement of biofilm formation, underscoring the key role of . Thermal shift assays showed ciprofloxacin binds purified AgrC protein, thereby inhibiting the Agr system. Molecular docking results further support the potential interaction between ciprofloxacin and AgrC. In summary, subinhibitory concentrations of ciprofloxacin stimulate biofilm formation via an -dependent pathway. This inductive effect may facilitate local infection establishment and bacterial persistence, ultimately leading to therapeutic failure.
ISSN:1664-302X
1664-302X
DOI:10.3389/fmicb.2023.1328947