Evidence map›Paper›PMID 38512984›Full record

ArticlePLoS genetics2024

Reciprocal regulation of enterococcal cephalosporin resistance by products of the autoregulated yvcJ-glmR-yvcL operon enhances fitness during cephalosporin exposure.

Dušanka Djorić, Samantha N Atkinson, Christopher J Kristich

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.4field-weighted citation impact, top 43% 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

2 citing papers in PubMed, 1 citations in OpenAlex.

  1. Article
  2. Staying in the loop to make ends meet: roles and regulation of GlmR inbioRxiv : the preprint server for biology · 2025
    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

3 authors at 1 institution in 1 country.

Dušanka DjorićDepartment of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.ORCID 0000-0002-9188-4213
Samantha N AtkinsonDepartment of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.ORCID 0000-0001-8571-8932
Christopher J KristichDepartment of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.ORCID 0000-0002-1660-0006
Medical College of Wisconsin · US

Funding

Role and regulation of peptidoglycan synthases in enterococcal antimicrobial resistanceR01AI150895 · NIAID · MEDICAL COLLEGE OF WISCONSIN · PI KRISTICH, CHRISTOPHER J · 2020 to 2024
$2.4M
Intrinsic cephalosporin resistance in enterococciR01AI134660 · NIAID · MEDICAL COLLEGE OF WISCONSIN · PI KRISTICH, CHRISTOPHER J · 2018 to 2021
$1.5M
NIAID NIH HHS R01 AI134660NIAID NIH HHS R01 AI150895
6 · The paper itself

Abstract

Enterococci are commensal members of the gastrointestinal tract and also major nosocomial pathogens. They possess both intrinsic and acquired resistance to many antibiotics, including intrinsic resistance to cephalosporins that target bacterial cell wall synthesis. These antimicrobial resistance traits make enterococcal infections challenging to treat. Moreover, prior therapy with antibiotics, including broad-spectrum cephalosporins, promotes enterococcal proliferation in the gut, resulting in dissemination to other sites of the body and subsequent infection. As a result, a better understanding of mechanisms of cephalosporin resistance is needed to enable development of new therapies to treat or prevent enterococcal infections. We previously reported that flow of metabolites through the peptidoglycan biosynthesis pathway is one determinant of enterococcal cephalosporin resistance. One factor that has been implicated in regulating flow of metabolites into cell wall biosynthesis pathways of other Gram-positive bacteria is GlmR. In enterococci, GlmR is encoded as the middle gene of a predicted 3-gene operon along with YvcJ and YvcL, whose functions are poorly understood. Here we use genetics and biochemistry to investigate the function of the enterococcal yvcJ-glmR-yvcL gene cluster. Our results reveal that YvcL is a DNA-binding protein that regulates expression of the yvcJ-glmR-yvcL operon in response to cell wall stress. YvcJ and GlmR bind UDP-GlcNAc and reciprocally regulate cephalosporin resistance in E. faecalis, and binding of UDP-GlcNAc by YvcJ appears essential for its activity. Reciprocal regulation by YvcJ/GlmR is essential for fitness during exposure to cephalosporin stress. Additionally, our results indicate that enterococcal GlmR likely acts by a different mechanism than the previously studied GlmR of Bacillus subtilis, suggesting that the YvcJ/GlmR regulatory module has evolved unique targets in different species of bacteria.

Indexed as

Cephalosporin ResistanceCephalosporinsAnti-Bacterial AgentsEnterococcus faecalisOperonUridine DiphosphateAnti-Bacterial AgentsCephalosporinsUridine Diphosphate

Identifiers

PMID38512984
PMCPMC10986989
OpenAlexW4393036368

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.