Evidence map›Paper›PMID 38942968›Full record

ArticleNature chemical biology2024

Potent and specific antibiotic combination therapy against Clostridioides difficile.

Vasiliki T Chioti, Kirklin L McWhorter, Tamra C Blue, Yuchen Li, Fei Xu, Philip D Jeffrey, Katherine M Davis, Mohammad R Seyedsayamdost

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature chemical biology, 2024. 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
–field-weighted citation impact
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.

  1. Article
  2. Frontiers in immunology · 2026
    Article
  3. Article
  4. Review
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.

Vasiliki T Chioti *Department of Chemistry, Princeton University, Princeton, NJ, USA.
Kirklin L McWhorter *Department of Chemistry, Emory University, Atlanta, GA, USA.
Tamra C BlueDepartment of Chemistry, Emory University, Atlanta, GA, USA.
Yuchen LiDepartment of Chemistry, Princeton University, Princeton, NJ, USA.
Fei XuInstitute of Pharmaceutical Biotechnology and Department of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.ORCID http://orcid.org/0000-0002-0372-5643
Philip D JeffreyDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.
Katherine M DavisDepartment of Chemistry, Princeton University, Princeton, NJ, USA. katherine.davis@emory.edu.ORCID http://orcid.org/0000-0002-0258-8907
Mohammad R SeyedsayamdostDepartment of Chemistry, Princeton University, Princeton, NJ, USA. mrseyed@princeton.edu.ORCID http://orcid.org/0000-0003-2707-4854

Funding

Unraveling the dynamics that enable unusual heme enzyme reactivityR35GM147557 · NIGMS · EMORY UNIVERSITY · PI Katherine Marie Davis · 2022 to 2026
$1.9M
Toward a Chemo-Enzymatic Synthesis of Vancomycin and Its AnalogsR01GM129496 · NIGMS · PRINCETON UNIVERSITY · PI SEYEDSAYAMDOST, MOHAMMAD R · 2019 to 2022
$1.2M
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) 1R01GM129496Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) 1R35GM147557NIGMS NIH HHS R01 GM129496NIGMS NIH HHS R35 GM147557
6 · The paper itself

Abstract

Keratinicyclins and keratinimicins are recently discovered glycopeptide antibiotics. Keratinimicins show broad-spectrum activity against Gram-positive bacteria, while keratinicyclins form a new chemotype by virtue of an unusual oxazolidinone moiety and exhibit specific antibiosis against Clostridioides difficile. Here we report the mechanism of action of keratinicyclin B (KCB). We find that steric constraints preclude KCB from binding peptidoglycan termini. Instead, KCB inhibits C. difficile growth by binding wall teichoic acids (WTAs) and interfering with cell wall remodeling. A computational model, guided by biochemical studies, provides an image of the interaction of KCB with C. difficile WTAs and shows that the same H-bonding framework used by glycopeptide antibiotics to bind peptidoglycan termini is used by KCB for interacting with WTAs. Analysis of KCB in combination with vancomycin (VAN) shows highly synergistic and specific antimicrobial activity, and that nanomolar combinations of the two drugs are sufficient for complete growth inhibition of C. difficile, while leaving common commensal strains unaffected.

Indexed as

Anti-Bacterial AgentsClostridioides difficileMicrobial Sensitivity TestsCell WallDrug Therapy, CombinationLipopeptidesPeptides, CyclicPeptidoglycanTeichoic AcidsVancomycinAnti-Bacterial AgentsCB-183,315LipopeptidesPeptides, CyclicPeptidoglycanTeichoic AcidsVancomycin

Identifiers

PMID38942968
PMCPMC11306116

What OpenQuestion holds

Textmetadata
LicenceTDM
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.