Tetracenomycin X novel inhibitor of translationстатьяТезисы
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Аннотация:Last few years people faced a problem that there are a lot new species of bacteria which could not been influenced by certain antibiotics. Also already known pathogenic bacteria gained resis- tance genes. Antibiotic resistance is one of the biggest threats to global health, according to WHO. By 2050, it is expected that mortality rate caused by bacterial diseases will increase 14 times. Therefore, there is great necessity of novel antibiotics in the whole world. Due to reasons mentioned above we decided to make screening for novel compounds with antibiotics activity. Screening was performed using reporter E. coli strain pDualrep2, which can detect translation inhibitors and DNA damaging antibiotics. In this screening we found significant antibiotic activ- ity for cultural broth sample of bacterium Amycolatopsis sp. which shown inhibition of translation. In further study a com- pound was purified by HPLC chromatography, the structure was determined by combination of NMR and mass spectrometry and it turned out, that we re-discovered old antibiotic - Tetraceno- mycin X (ThX). However, a mechanism of antibiotic activity has not elucidated yet. Further study showed that in vitro translation with this compound shows opportunity to decrease level of trans- lation. This result was proved by toe-printing assay, which demonstrates a translational inhibition as well. By now we also have found some mutant strains of E. coli which have ThX resis- tance because of mutations in rRNA, this data is also proved by probing assay. Therefore, it could be reasonably assumed that ThX probably provides inhibition of translation on elongation stage. In view of all data obtained, Tetracenomycin X is of great medical and scientific interest as a molecule which might be a basis to development of novel antibiotic drug. Thereby it requires a further scrutiny. Work was supported by the Russian Science Foundation (grant 18-44-04005) for I.A.O.