发布者:抗性基因网 时间:2019-01-03 浏览量:540
摘要
抗生素耐药性有可能在全球范围内有效治疗微生物感染。这种情况促使学术界和制药业寻找新的抗菌化合物。在这里,我们报告了广泛使用的抗肿瘤药物顺铂如何被重新利用作为对医院病原体铜绿假单胞菌的有效抗菌药物。发现顺铂有效杀死铜绿假单胞菌菌株。在这样的实验中,转录组学分析显示recA基因的上调,已知其对DNA修复是重要的,暗示顺铂可干扰铜绿假单胞菌中的DNA复制。顺铂治疗显着抑制III型分泌系统(T3SS),其对外毒素的分泌很重要。此外,还证明顺铂在小鼠角膜炎模型中根除体外生物膜和体内生物膜。这表明顺铂可以有效地用于根除生物膜感染,否则传统抗生素难以治疗。尽管顺铂在全身暴露时对人体具有高毒性,但局部治疗证明其具有低毒性。这表明顺铂的高于最小抑制浓度(MIC)剂量可以局部应用于治疗持续性和顽固性铜绿假单胞菌感染。
Antibiotic resistance threatens effective treatment of microbial infections globally. This situation has spurred the hunt for new antimicrobial compounds in both academia and the pharmaceutical industry. Here, we report how the widely used antitumor drug cisplatin may be repurposed as an effective antimicrobial against the nosocomial pathogen Pseudomonas aeruginosa. Cisplatin was found to effectively kill strains of P. aeruginosa. In such experiments, transcriptomic profiling showed upregulation of the recA gene, which is known to be important for DNA repair, implicating that cisplatin could interfere with DNA replication in P. aeruginosa. Cisplatin treatment significantly repressed the type III secretion system (T3SS), which is important for the secretion of exotoxins. Furthermore, cisplatin was also demonstrated to eradicate in vitro biofilms and in vivo biofilms in a murine keratitis model. This showed that cisplatin could be effectively used to eradicate biofilm infections which were otherwise difficult to be treated by conventional antibiotics. Although cisplatin is highly toxic for humans upon systemic exposure, a low toxicity was demonstrated with topical treatment. This indicated that higher-than-minimal inhibitory concentration (MIC) doses of cisplatin could be topically applied to treat persistent and recalcitrant P. aeruginosa infections.
https://www.ncbi.nlm.nih.gov/pubmed/30591828