Abstract

Antibiotic resistance is one of the greatest problems in modern medicine and a global threat to health care. Aminoglycoside phosphotransferases (APHs) currently pose a serious threat to antimicrobial therapy; therefore, research on the functions and obtainment of 3D structures of aminoglycoside phosphotransferases is an important and urgent issue that will allow the development of approaches to overcome resistance to aminoglycoside antibiotics. Soil actinobacteria of the Streptomyces genus contain the largest number of aph genes; these genes can be transferred to them from antibiotic producing strains. The review analyzes the current data on the actinobacteria of the Streptomyces genus as a reservoir of drug resistance genes, as well as approaches to the identification of aph genes associated with resistance to aminoglycoside antibiotics on the example of the model strain S. rimosus ATCC 10970 (oxytetracycline producer). The data on the development of test systems for the screening of inhibitors and potential drugs are discussed. The inhibition of proteins that provide a natural level of bacterial resistance to a number of aminoglycoside antibiotics may help overcome multidrug resistance in pathogenic actinobacteria and expand the range of drugs used due to the synergistic effect of the antibiotic with the ARH inhibitor compound.

中文翻译：

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链霉菌属土壤细菌中氨基糖苷磷酸转移酶基因

摘要

抗生素耐药性是现代医学中最大的问题之一，也是对卫生保健的全球威胁。氨基糖苷磷酸转移酶（APHs）目前对抗菌治疗构成了严重威胁。因此，研究氨基糖苷磷酸转移酶的功能和3D结构的获得是重要而紧迫的问题，这将允许开发克服对氨基糖苷抗生素耐药性的方法。链霉菌属的土壤放线菌包含最大数量的aph基因。这些基因可以从产生抗生素的菌株中转移到它们身上。该评论分析了链霉菌放线菌的最新数据属作为药物抗性基因的贮藏库，以及在模型菌株S.rimosus ATCC 10970（土霉素）生产实例中鉴定与对氨基糖苷类抗生素抗性相关的aph基因的方法。讨论了用于筛选抑制剂和潜在药物的测试系统的开发数据。抑制对多种氨基糖苷类抗生素具有天然细菌抵抗力的蛋白质，由于抗生素与ARH抑制剂化合物的协同作用，可能有助于克服病原性放线菌中的多药耐药性，并扩大药物使用范围。