Histidine-triad hydrolases provide resistance to peptide- nucleotide antibiotics

Eldar Yagmurov, Darya Tsibulskaya, Alexey Livenskyi, Marina Serebryakova, Yury I. Wolf, Sergei Borukhov, Konstantin Severinov, Svetlana Dubiley

    Результат исследований: Вклад в журналСтатьярецензирование

    4 Цитирования (Scopus)

    Аннотация

    The Escherichia coli microcin C (McC) and related compounds are potent Trojan horse peptide-nucleotide antibiotics. The peptide part facilitates transport into sensitive cells. Inside the cell, the peptide part is degraded by nonspecific peptidases releasing an aspartamide-adenylate containing a phosphoramide bond. This nonhydrolyzable compound inhibits aspartyl-tRNA synthetase. In addition to the efficient export of McC outside the producing cells, special mechanisms have evolved to avoid self-toxicity caused by the degradation of the peptide part inside the producers. Here, we report that histidine-triad (HIT) hydrolases encoded in biosynthetic clusters of some McC homologs or by standalone genes confer resistance to McC-like compounds by hydrolyzing the phosphoramide bond in toxic aspartamide-adenosine, rendering them inactive. IMPORTANCE Uncovering the mechanisms of resistance is a required step for countering the looming antibiotic resistance crisis. In this communication, we show how universally conserved histidine-triad hydrolases provide resistance to microcin C, a potent inhibitor of bacterial protein synthesis.

    Язык оригиналаАнглийский
    Номер статьиe00497-20
    ЖурналmBio
    Том11
    Номер выпуска2
    DOI
    СостояниеОпубликовано - 1 мар. 2020

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