Higazy Doaa, Ahmed Marwa N, Ciofu Oana
Costerton Biofilm Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, 2200, Denmark.
Department of Microbiology, Faculty of Agriculture, Cairo University, Giza, 12613, Egypt.
NPJ Biofilms Microbiomes. 2024 Dec 30;10(1):156. doi: 10.1038/s41522-024-00640-3.
The evolution of antimicrobial resistance (AMR) in biofilms, driven by mechanisms like oxidative stress, is a major challenge. This study investigates whether antioxidants (AOs) such as N-acetyl-cysteine (NAC) and Edaravone (ED) can reduce AMR in Pseudomonas aeruginosa biofilms exposed to sub-inhibitory concentrations of ciprofloxacin (CIP). In vitro experimental evolution studies were conducted using flow cells and glass beads biofilm models. Results showed that combining CIP with antioxidants (CIP-AOs) effectively reduced the development of CIP resistance. Isolates from biofilms treated with CIP-AO had significantly lower minimum inhibitory concentrations (MICs) of CIP compared to those treated with CIP alone. Whole-genome sequencing (WGS) revealed mutations in the negative regulators of efflux pumps, nfxB, and nalC, in CIP-only treated biofilm populations. The occurrence of nfxB mutations was significantly lower in flow cell biofilms treated with CIP-AO compared to CIP alone. These findings suggest that antioxidants could play a role in mitigating AMR development in biofilms.
由氧化应激等机制驱动的生物膜中抗菌药物耐药性（AMR）的演变是一项重大挑战。本研究调查了诸如N-乙酰半胱氨酸（NAC）和依达拉奉（ED）等抗氧化剂（AO）是否能够降低暴露于亚抑制浓度环丙沙星（CIP）的铜绿假单胞菌生物膜中的AMR。使用流动小室和玻璃珠生物膜模型进行了体外实验进化研究。结果表明，将CIP与抗氧化剂（CIP-AO）联合使用可有效降低CIP耐药性的产生。与仅用CIP处理的生物膜相比，用CIP-AO处理的生物膜分离株的CIP最低抑菌浓度（MIC）显著更低。全基因组测序（WGS）显示，仅用CIP处理的生物膜群体中，外排泵的负调控因子nfxB和nalC发生了突变。与仅用CIP处理相比，用CIP-AO处理的流动小室生物膜中nfxB突变的发生率显著更低。这些发现表明，抗氧化剂可能在减轻生物膜中AMR的发展方面发挥作用。
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