Combined Action of Cerium Oxide Nanoparticles and Ciprofloxacin Against Staphylococcus aureus: Driving Mechanisms

Abstract

The rise of antimicrobial resistance has intensified the need for alternative strategies to enhance antibiotic efficacy. Cerium oxide nanoparticles (CeO₂ NPs) have shown promise as antimicrobial agents; however, their potential in combination with antibiotics remains underexplored. To elucidate the mechanisms underlying the synergistic antibacterial effects of CeO₂ NPs with ciprofloxacin against Staphylococcus aureus, we conducted detailed mechanistic investigations. CeO₂ NPs were synthesized using a non- isothermal precipitation method and characterized via scanning electron microscopy (SEM), X-ray diffraction (XRD), and dynamic light scattering (DLS). Antibacterial activity was evaluated through minimum inhibitory concentration (MIC) assays. Mechanistic studies included bacterial growth curve analysis, ROS quantification, and SEM imaging of treated bacterial cells. CeO₂ NPs exhibited an additive effect with ciprofloxacin, reducing its MIC by threefold. Mechanistic investigations revealed that CeO₂ NPs disrupted bacterial membrane integrity, induced oxidative stress through ROS overproduction, and significantly prolonged bacterial doubling time. SEM analysis confirmed extensive structural damage, including cell wall disruption and cytoplasmic leakage. These findings highlight the dual antibacterial role of CeO₂ NPs: direct bacterial damage and enhancement of ciprofloxacin's efficacy. CeO₂ NPs hold potential as antibiotic adjuvants to combat resistant Gram-positive infections. Further studies should focus on optimizing nanoparticle formulations, evaluating in vivo efficacy, and assessing their clinical translation to address the global challenge of antimicrobial resistance.

Keywords

• Antibacterial activity
• Cerium oxide nanoparticles (CeO₂ NPs)
• Ciprofloxacin
• Synergy

Supporting Institution

Scientific and Technological Research Council of Turkey

Project Number

#319S024

Thanks

The authors acknowledge financial support from the Scientific and Technological Research Council of Türkiye (TÜBİTAK; project no. 319S024). We thank Doğa Vural for preparing the content of Scheme 1. Didem Şen Karaman acknowledges support from the Turkish Academy of Sciences through the Outstanding Young Scientists Award Program (TÜBA-GEBİP 2023). Ayşenur Pamukçu acknowledges support from the TÜBİTAK BİDEB 2211-A Scholarship Programme and the Council of Higher Education’s 100/2000 Doctoral Scholarship Programme. Emine Hilal Altıntop acknowledges support from the Can Sağlığı Foundation scholarship programme.

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