Heterologous production of AmiN kinase provides the resistance of mammalian cells toward ribosome-targeting antibiotic amicoumacin

Danilov, D.; S, T.; Smirnov, I.V.

Авторы: Danilov D., S Terekhov, Smirnov I.V.
Журнал: FEBS open bio
Номер: 11
Год издания: 2021
Издательство: John Wiley & Sons Inc.
Местоположение издательства: United States
Первая страница: 266
DOI: 10.1002/2211-5463.13205
Аннотация: Amicoumacin A (Ami) is a broad-spectrum antibiotic displayingan inhibitory effect on protein translation by the disintegrationof initiation complex array and the shifting of mRNA-tRNAcomplex motion during relocation. Ami exhibits not only strongantimicrobial properties but also potent anti-inﬂammatory,antiulcer and antitumor activity. The study of the biosyntheticgene cluster of the Ami producing strain Bacillus pumilus 124 ledto the discovery of the self-resistance kinase AmiN inactivatingAmi by phosphorylation that is reversed in vivo by the respectivephosphatase AmiO. Here we evaluated the effect of heterologous expression of amiN on the resistance of prokaryotic and eukaryotic cells toward Ami. Preliminary evaluation of Ami antibacte-rial potential was performed on the model E. coli ∆tolC cells highly sensitive to different antimicrobials. The heterologous expression of amiN increased the minimum inhibitory concentration (MIC) of Ami by 100 times in this model bacterium. Similarly, the transfection of HEK293-T cells with a genetic construct containing the amiN gene elevated the half-maximal inhibitory concentration (IC50) of Ami by more than 300 folds, assessed by the MTT-test and ﬂow cytometry. Thus, we suggest that a remarkable difference in inhibitory concentrations between wild type and recombinant cells ensures high selection efﬁciency. Webelieve that the described anti-Ami activity will provide essential insight into the antibiotic resistance problem and ﬁnd numerous applications in the ﬁeld of synthetic biology and biotechnology.This work is supported by RSF grant 19-14-00331.
Добавил в систему: Бачева Анна Владимировна

	ИСТИНА	Войти в систему Регистрация
	Интеллектуальная Система Тематического Исследования НАукометрических данных
	Главная Поиск Статистика О проекте Помощь

ИСТИНА

Интеллектуальная Система Тематического Исследования НАукометрических данных

Heterologous production of AmiN kinase provides the resistance of mammalian cells toward ribosome-targeting antibiotic amicoumacinстатья Тезисы

Прикрепленные файлы