Scientists have discovered a new high-level drug resistance mechanism for metastasis cyclin

May 28th, the journal Nature Microbiology published a research paper entitled "Built of plasmid-mediated high-level tigecycline resistance in animals and humans" by a team of academicians from the Agricultural University of China.
-cyclin is the third generation of medical-specific tyrencline drugs developed by Wyeth corporation in the United States, listed in China in 2011, the World Health Organization (WHO) listed it as the treatment of clinical multi-drug-resistant bacterial infections extremely important antimicrobial drugs for skin and skin tissue infections and complex intracella abdominal infection treatment. In the current medical clinical multi-drug-resistant Terranean-negative bacteria on carbon penicillin increasingly severe situation, tygacycline and another peptide drug polymycin has become one of the few options for the treatment of the above-mentioned infections. In recent years, however, the task force has reported for the first time the generation, transmission and risk analysis of the transferable polymicrobial-resistant gene mcr-1 (published in Lancet Infectious Disease 2016, 2017; Nature Microbiology 2018), making tygacycline the "last line of defense" for the true treatment of "superbug" infections.
in view of the importance of cyclocycline in the medical clinic, Shen Jianzhong academician team in recent years has been monitoring the resistance of important pathogens to cyclocycline. Through unremitting efforts, the team, in cooperation with researchers from the Jiangsu Academy of Agricultural Sciences, found one strain each carrying the Tate (X) gene variants of Baumann and E. coli in pig source samples, and the encoded proteins were 85.1% and 93.8% homogenic, respectively, with the wild TatX found, so they were named Tat (X3) and Tt (X4). Subsequently, the team used functional cloning, protein three-stage structure prediction, molecular docking, supplemented by protease dynamics, mass spectrometry and nuclear magnetic resonance and other technical methods to verify the modification function of two new variants of tetrycline drugs (Figure 1).Compared to wild TatX, these two variants not only mediate high levels of resistance of wild strains to cyclocycline (minimum antibacterial concentrations of 32-64 mg l
), but also two newly approved new teretin-type drugs, eravacycline and omadacycline, to the U.S. Food and Drug Administration. The two new drugs, as alternatives to cyclocycline, have better antibacterial activity and small side effects than cyclocycline and are not yet available in China. Gene transfer studies have shown that tet(X3) and tet (X4) are located on the multi-drug-resistant plasmids of bacteria and can be transferred through joint transfer into clinically important pathogens such as Crebbs, Bowman's and E. coli. What's more, animal trial models have confirmed that tate(X) variants can lead to the failure of clinically tetracycline to treat infections that carry the drug-resistant gene pathogen (Figure 2). Epidemiological retrospective studies showed that tate (X3) and tat (X4) had an average detection rate of 6.9% in domestic animal and food-sourced bacteria, with some areas having a detection rate of 66.7% for E. coli, and five bovine-sourced immobilized bacteria carrying the carbon penicillin-resistant genes blaNDM-1 and Tt (X3). In addition, the team also detected tat (X4) from 3 strains of E. coli and 1 strain of Bowman P. coli, and although the detection rate was low (0.07%), the risk could not be ignored.particular attention is that these two new tit(X) variants also have cross-resistance, which can be mediated to traditional first- and second-generation tetricytacytope drugs. At present, the first- and second-generation tylutin drugs, represented by kimmycin, tomycin and docetonin, are the largest antibacterial drugs used in livestock and poultry farming industry, and are widely used in animal and poultry growth and preventive treatment. Strong drug selection stress may promote the abunding and transfer of tate(X) variants and the bacteria they carry in livestock and poultry and in the breeding environment, increasing their likelihood of transmission through the food chain or the environment. Therefore, this study also serves as a warning effect on the use of tectonthycin drugs, especially kimmycin and tomycin, as growth promoters in livestock and poultry farming, and further research should be used to assess the risks of use of these drugs in food animals.
Dr. He Tao, Researcher Wang Ran and Liu Dejun, Ph.D., Agricultural University of China, are co-authors of this research paper, and Wang Yang and Shen Jianzhong, professors of animal medicine at Agricultural University of China and post-scientists at the Beijing Center for High-Sophisticated Innovation in Food Nutrition and Human Health, are co-authors of this paper. This research has received the ministry of science and technology "13th Five-Year Plan" national key research and development program key special, the National Natural Science Foundation of China-UK "international cooperation project" and the Ministry of Agriculture related special support. (Source: Science Network)
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