Genes of Aminoglycoside Phosphotransferases in Soil Bacteria of the Streptomyces Genus
- PDF / 1,162,104 Bytes
- 13 Pages / 612 x 792 pts (letter) Page_size
- 38 Downloads / 134 Views
s of Aminoglycoside Phosphotransferases in Soil Bacteria of the Streptomyces Genus N. N. Rudakovaa, *, M. G. Alekseevaa, and V. N. Danilenkoa aVavilov
Institute of General Genetics, Russian Academy of Sciences, Moscow, 117971 Russia *e-mail: [email protected] Received January 14, 2020; revised January 14, 2020; accepted January 14, 2020
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. Keywords: aminoglycoside phosphotransferase (APH), natural resistance to aminoglycoside antibiotics, Streptomyces rimosus, 3D protein structures, screening of inhibitors DOI: 10.1134/S2079086420060055
INTRODUCTION Antibiotic resistance is one of the greatest problems in modern medicine and a global threat to health care. According to the data of the Centers for Disease Control and Prevention, at least 2 million people are infected with antibiotic resistant bacteria, and at least 7.23 million people die annually from diseases caused by antibiotic resistant microorganisms (Hossion and Sasaki, 2013). The World Health Organization (WHO) asked the UN to discuss this problem and to adopt appropriate recommendations. The problem is determined not only by the catastrophic spread of clinical strains of multidrug-resistant (MDR) bacteria, but also by the spread of MDR bacteria in food, farm animals, and plants, as well as in soil and water sources (Link et al., 2007). Thus, it is relevant to study soil bacteria as the main reservoir and a possible source of drug-resistance genes (Gibson et al., 2015). Aminoglycosides represent a large group of biologically active, secondary metabolites (Davies and Wright, 1997). Since the discovery of this group of antibacterial drugs, they have been widely used as a therapeutic agent in the treatment of various severe inf
Data Loading...
