Evidence map›Paper›PMID 37097175›Full record

ArticleAntimicrobial agents and chemotherapy2023

Combining Signal Peptidase and Lipoprotein Processing Inhibitors Overcomes Ayr Resistance in Staphylococcus aureus.

Madeleine C Stone, Aaron Mychack, Kathryn A Coe, Suzanne Walker

Open access · greenAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.0field-weighted citation impact, top 27% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. A diverse single-stranded DNA-annealing protein library enables efficient genome editing across bacterial phyla.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  2. Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025
    Review
  3. Review
  4. 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

4 authors at 1 institution in 1 country.

Madeleine C StoneDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0001-6886-6589
Aaron MychackDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0003-3983-3889
Kathryn A CoeDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.
Suzanne WalkerDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0002-0545-914X
Harvard University · US

Funding

Technical Mother Machine CoreP01AI083214 · NIAID · SCHEPENS EYE RESEARCH INSTITUTE · PI David C Hooper · 2009 to 2026
$39.4M
Release of Extracellular DNA during Biofilm Formation in Staphylococcus aureusR01AI139011 · NIAID · HARVARD UNIVERSITY · PI KAHNE, DANIEL, LOSICK, RICHARD MARC · 2018 to 2022
$3.2M
NIAID NIH HHS P01 AI083214NIAID NIH HHS R01 AI139011
6 · The paper itself

Abstract

Antibiotic resistance in bacterial pathogens is an ongoing public health concern. The arylomycins are a class of natural product antibiotics that target the type I signal peptidase, which carries out the terminal step in protein secretion. Here, we used transposon sequencing (Tn-Seq) to profile the effects of the optimized arylomycin derivative G0775 in Staphylococcus aureus. Our transposon libraries include both upregulation and inactivation mutants, allowing us to identify resistance mechanisms and targets for synergism. We identified several cell envelope pathways that, when inactivated, sensitize S. aureus to the arylomycin G0775. These pathways include the lipoprotein processing pathway, and we have shown that inhibitors of this pathway synergize with G0775 even though lipoprotein processing is nonessential in S. aureus. Moreover, we found that blocking this pathway completely reverses Ayr resistance, which is a major resistance mechanism to arylomycins, including G0775. Our Tn-Seq data also showed that upregulation of

Indexed as

DaptomycinStaphylococcal InfectionsAnti-Bacterial AgentsBacterial ProteinsHumansMembrane ProteinsMicrobial Sensitivity TestsSerine EndopeptidasesStaphylococcus aureusAnti-Bacterial AgentsBacterial ProteinsDaptomycinMembrane ProteinsSerine Endopeptidasestype I signal peptidaseantibiotic resistancearylomycinsecretionsignal peptidase

Identifiers

PMID37097175
PMCPMC10190671
OpenAlexW4366984010

What OpenQuestion holds

Textmetadata
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.