Gao Fanglin, Xiang Wanquan, Zhang Xiaoyan, Huang Xiaoxing, She Feifei, Wen Yancheng
Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China.
Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China.
Front Med (Lausanne). 2025 Jul 21;12:1552537. doi: 10.3389/fmed.2025.1552537. eCollection 2025.
infection is a significant risk factor for various gastrointestinal diseases, while the standard triple therapy for its eradication is increasingly compromised by antibiotic resistance. This study investigates the role of the CrdAB-CzcBA efflux pump and its regulation by copper in tetracycline resistance in . Using minimum inhibitory concentration (MIC) determination and growth curve analysis, we found that the deletion of or significantly reduced tetracycline resistance, while overexpression of CrdAB-CzcBA under the urease promoter enhanced bacterial resistance by reducing intracellular tetracycline accumulation. Ethidium bromide and tetracycline accumulation assays confirmed that CrdAB-CzcBA mediates active efflux of tetracycline, contributing to reduced intracellular drug levels. Furthermore, copper supplementation upregulated the expression of CrdAB-CzcBA via the CrdRS two-component system, thereby promoting bacterial growth under tetracycline stress. Notably, copper-induced resistance was abrogated in Δ mutants, demonstrating the dependence of this mechanism on CrdRS. These findings highlight CrdAB-CzcBA as a critical efflux system in tetracycline resistance and emphasize the role of environmental factors, such as copper, in modulating bacterial antibiotic resistance, underscoring the need for strategies that account for metal ion influences in managing infections.
感染是多种胃肠道疾病的重要风险因素，而用于根除感染的标准三联疗法正日益受到抗生素耐药性的影响。本研究调查了CrdAB - CzcBA外排泵及其受铜调控在[具体细菌名称未给出]对四环素耐药性中的作用。通过最小抑菌浓度（MIC）测定和生长曲线分析，我们发现缺失[具体基因名称未给出]或[具体基因名称未给出]会显著降低四环素耐药性，而在脲酶启动子下过表达CrdAB - CzcBA通过减少细胞内四环素积累增强了细菌耐药性。溴化乙锭和四环素积累试验证实CrdAB - CzcBA介导四环素的主动外排，导致细胞内药物水平降低。此外，补充铜通过CrdRS双组分系统上调CrdAB - CzcBA的表达，从而在四环素应激下促进细菌生长。值得注意的是，在Δ[具体基因名称未给出]突变体中铜诱导的耐药性被消除，表明该机制对CrdRS的依赖性。这些发现突出了CrdAB - CzcBA作为四环素耐药性中的关键外排系统，并强调了环境因素如铜在调节细菌抗生素耐药性中的作用，强调了在管理[具体细菌名称未给出]感染时需要考虑金属离子影响的策略。
