Department of Pathogen Biology & Jiangsu Key Laboratory of Pathogen Biology & Helicobacter pylori Research Centre, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
Department of Gastroenterology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
Microb Biotechnol. 2022 Feb;15(2):442-454. doi: 10.1111/1751-7915.13807. Epub 2021 Mar 29.
Antibiotic resistance in Helicobacter pylori has been growing worldwide with current treatment regimens. Development of new compounds for treatment of H. pylori infections is urgently required to achieve a successful eradication therapy in the future. Armeniaspirols, a novel class of natural products isolated from Streptomyces armeniacus, have been previously identified as antibacterial agents against Gram-positive pathogens. In this study, we found that armeniaspirol A (ARM1) exhibited potent antibacterial activity against H. pylori, including multidrug-resistant strains, with MIC range values of 4-16 μg ml . The underlying mechanism of action of ARM1 against H. pylori involved the disruption of bacterial cell membranes. Also, ARM1 inhibited biofilm formation, eliminated preformed biofilms and killed biofilm-encased H. pylori in a dose-dependent manner. In a mouse model of multidrug-resistant H. pylori infection, dual therapy with ARM1 and omeprazole showed efficient in vivo killing efficacy comparable to the standard triple therapy, and induced negligible toxicity against normal tissues. Moreover, at acidic pH 2.5, ARM1 exhibited a much more potent anti-H. pylori activity than metronidazole. Thus, these findings demonstrated that ARM1 is a novel potent anti-H. pylori agent, which can be developed as a promising drug lead for treatment of H. pylori infections.
幽门螺杆菌的抗生素耐药性在全球范围内不断增加，当前的治疗方案也面临挑战。为了实现未来成功的根除治疗，迫切需要开发新的化合物来治疗幽门螺杆菌感染。Armeniaspirols 是从链霉菌属中分离出来的一种新型天然产物，先前已被鉴定为针对革兰氏阳性病原体的抗菌剂。在这项研究中，我们发现 armeniaspirol A（ARM1）对幽门螺杆菌具有强大的抗菌活性，包括对多种耐药菌株的 MIC 范围值为 4-16μg/ml。ARM1 对幽门螺杆菌的作用机制涉及破坏细菌细胞膜。此外，ARM1 还能抑制生物膜的形成，消除已形成的生物膜，并以剂量依赖的方式杀死生物膜包裹的幽门螺杆菌。在多药耐药幽门螺杆菌感染的小鼠模型中，ARM1 与奥美拉唑的联合治疗显示出与标准三联疗法相当的体内杀菌效果，并且对正常组织的毒性可忽略不计。此外，在酸性 pH 2.5 条件下，ARM1 对幽门螺杆菌的活性比甲硝唑强得多。因此，这些发现表明 ARM1 是一种新型有效的抗幽门螺杆菌药物，可作为治疗幽门螺杆菌感染的有前途的药物先导化合物。
