Histidine-Triad Hydrolases Provide Resistance to Peptide-Nucleotide Antibioticsстатья
Статья опубликована в высокорейтинговом журнале
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Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 2 сентября 2020 г.
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.