Evidence map›Paper›PMID 35852818›Full record

ArticleAngewandte Chemie (International ed. in English)2022

A Specialized Polythioamide-Binding Protein Confers Antibiotic Self-Resistance in Anaerobic Bacteria.

Finn Gude, Evelyn M Molloy, Therese Horch, Maria Dell, Kyle L Dunbar, Jana Krabbe, Michael Groll, Christian Hertweck

Open access · hybridAbstract read
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.1field-weighted citation impact, top 64% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Finn GudeResearch Unit Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Adolf-Reichwein-Straße 23, 07745, Jena, Germany.ORCID 0000-0002-8038-5937
Evelyn M MolloyResearch Unit Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Adolf-Reichwein-Straße 23, 07745, Jena, Germany.ORCID 0000-0001-8822-7207
Therese HorchResearch Unit Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Adolf-Reichwein-Straße 23, 07745, Jena, Germany.ORCID 0000-0002-3705-9423
Maria DellResearch Unit Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Adolf-Reichwein-Straße 23, 07745, Jena, Germany.ORCID 0000-0003-2718-2409
Kyle L DunbarResearch Unit Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Adolf-Reichwein-Straße 23, 07745, Jena, Germany.ORCID 0000-0002-7410-5169
Jana KrabbeResearch Unit Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Adolf-Reichwein-Straße 23, 07745, Jena, Germany.ORCID 0000-0003-3510-8276
Michael GrollCenter for Protein Assemblies, Technical University of Munich, Ernst-Otto-Fischer-Straße 8, 85747, Garching, Germany.ORCID 0000-0002-1660-340X
Christian HertweckResearch Unit Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Adolf-Reichwein-Straße 23, 07745, Jena, Germany.ORCID 0000-0002-0367-337X
Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) · DEFischer (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Understanding antibiotic resistance mechanisms is central to the development of anti-infective therapies and genomics-based drug discovery. Yet, many knowledge gaps remain regarding the resistance strategies employed against novel types of antibiotics from less-explored producers such as anaerobic bacteria, among them the Clostridia. Through the use of genome editing and functional assays, we found that CtaZ confers self-resistance against the copper chelator and gyrase inhibitor closthioamide (CTA) in Ruminiclostridium cellulolyticum. Bioinformatics, biochemical analyses, and X-ray crystallography revealed CtaZ as a founding member of a new group of GyrI-like proteins. CtaZ is unique in binding a polythioamide scaffold in a ligand-optimized hydrophobic pocket, thereby confining CTA. By genome mining using CtaZ as a handle, we discovered previously overlooked homologs encoded by diverse members of the phylum Firmicutes, including many pathogens. In addition to characterizing both a new role for a GyrI-like domain in self-resistance and unprecedented thioamide binding, this work aids in uncovering related drug-resistance mechanisms.

Indexed as

Bacteria, AnaerobicCarrier ProteinsAnti-Bacterial AgentsDrug Resistance, MicrobialGene EditingAnti-Bacterial AgentsCarrier ProteinsAntibioticsNatural ProductsNonribosomal PeptideResistanceThioamide

Identifiers

PMID35852818
PMCPMC9545259
OpenAlexW4285794579

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.