National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Single-Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics, Shandong Energy Institute, Qingdao New Energy Shandong Laboratory, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China.
Helicobacter. 2024 Sep-Oct;29(5):e13136. doi: 10.1111/hel.13136.
Metronidazole is a first-line antibiotic to treat Helicobacter pylori infections. However, the Clinical Laboratory Standards Institute guidelines recommend against using antimicrobial susceptibility test (AST) to test metronidazole resistance, due to the unreliable predictive power which can result in treatment failure.
The aim of this study was to establish an 8-h, metabolic-phenotype based AST for H. pylori metronidazole susceptibility using DO-probed Raman microspectroscopy.
Minimal inhibitory concentration (MIC) measured by conventional AST (E-test) were compared with expedited MIC via metabolic activity (eMIC-MA) for 10 H. pylori isolates. Raman barcodes of cellular-response to stress (RBCS) incorporating protein and carbohydrate Raman bands, were utilized to identify a biomarker to distinguish metronidazole susceptibility.
Specifically, eMIC-MA produces metronidazole susceptibility results showing 100% agreement with E-test, and determines the bactericidal dosage for both high- and low-level resistant H. pylori strains. In addition, RBCS not just reliably distinguish between metronidazole-susceptible and -resistant strains, but reveal their distinct mechanisms in bacterial responses to metronidazole.
The speed, accuracy, low cost, and rich information content that reveals the mode-of-action of drugs suggest the method's value in guiding metronidazole prescriptions for H. pylori eradication and in rapid screening based on drug-resistance mechanism.
甲硝唑是治疗幽门螺杆菌感染的一线抗生素。然而，由于预测能力不可靠，可能导致治疗失败，临床实验室标准协会指南建议不要使用抗菌药物敏感性试验（AST）来检测甲硝唑耐药性。
本研究旨在建立一种基于 8 小时代谢表型的 DO 探针拉曼光谱法 AST，用于检测幽门螺杆菌对甲硝唑的敏感性。
通过传统 AST（E 试验）测量最小抑菌浓度（MIC），并与代谢活性（eMIC-MA）进行比较，共对 10 株幽门螺杆菌进行了比较。细胞应激反应的拉曼条码（RBCS），结合蛋白质和碳水化合物的拉曼带，用于鉴定一个生物标志物来区分甲硝唑的敏感性。
具体来说，eMIC-MA 产生的甲硝唑敏感性结果与 E 试验完全一致，并确定了高低水平耐药幽门螺杆菌菌株的杀菌剂量。此外，RBCS 不仅可靠地区分了甲硝唑敏感和耐药菌株，而且还揭示了它们在细菌对甲硝唑的反应中的不同机制。
该方法速度快、准确性高、成本低，并且包含丰富的药物作用模式信息，这表明该方法在指导甲硝唑治疗幽门螺杆菌根除和基于耐药机制的快速筛选方面具有重要价值。
