Histidine-Triad Hydrolases Provide Resistance to Peptide-Nucleotide Antibiotics

ABSTRACT 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 contain...

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Autores principales:	Eldar Yagmurov, Darya Tsibulskaya, Alexey Livenskyi, Marina Serebryakova, Yury I. Wolf, Sergei Borukhov, Konstantin Severinov, Svetlana Dubiley
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	HinT RiPPs antibiotics histidine-triad proteins microcin C peptide-nucleotides Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b80e8b2de51b4e6eac6f5593db304134
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spelling	oai:doaj.org-article:b80e8b2de51b4e6eac6f5593db3041342021-11-15T15:57:03ZHistidine-Triad Hydrolases Provide Resistance to Peptide-Nucleotide Antibiotics10.1128/mBio.00497-202150-7511https://doaj.org/article/b80e8b2de51b4e6eac6f5593db3041342020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00497-20https://doaj.org/toc/2150-7511ABSTRACT 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.Eldar YagmurovDarya TsibulskayaAlexey LivenskyiMarina SerebryakovaYury I. WolfSergei BorukhovKonstantin SeverinovSvetlana DubileyAmerican Society for MicrobiologyarticleHinTRiPPsantibioticshistidine-triad proteinsmicrocin Cpeptide-nucleotidesMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	HinT RiPPs antibiotics histidine-triad proteins microcin C peptide-nucleotides Microbiology QR1-502
spellingShingle	HinT RiPPs antibiotics histidine-triad proteins microcin C peptide-nucleotides Microbiology QR1-502 Eldar Yagmurov Darya Tsibulskaya Alexey Livenskyi Marina Serebryakova Yury I. Wolf Sergei Borukhov Konstantin Severinov Svetlana Dubiley Histidine-Triad Hydrolases Provide Resistance to Peptide-Nucleotide Antibiotics
description	ABSTRACT 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.
format	article
author	Eldar Yagmurov Darya Tsibulskaya Alexey Livenskyi Marina Serebryakova Yury I. Wolf Sergei Borukhov Konstantin Severinov Svetlana Dubiley
author_facet	Eldar Yagmurov Darya Tsibulskaya Alexey Livenskyi Marina Serebryakova Yury I. Wolf Sergei Borukhov Konstantin Severinov Svetlana Dubiley
author_sort	Eldar Yagmurov
title	Histidine-Triad Hydrolases Provide Resistance to Peptide-Nucleotide Antibiotics
title_short	Histidine-Triad Hydrolases Provide Resistance to Peptide-Nucleotide Antibiotics
title_full	Histidine-Triad Hydrolases Provide Resistance to Peptide-Nucleotide Antibiotics
title_fullStr	Histidine-Triad Hydrolases Provide Resistance to Peptide-Nucleotide Antibiotics
title_full_unstemmed	Histidine-Triad Hydrolases Provide Resistance to Peptide-Nucleotide Antibiotics
title_sort	histidine-triad hydrolases provide resistance to peptide-nucleotide antibiotics
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/b80e8b2de51b4e6eac6f5593db304134
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Histidine-Triad Hydrolases Provide Resistance to Peptide-Nucleotide Antibiotics

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