Evidence map›Paper›PMID 39361718›Full record

ArticlePLoS pathogens2024

The five homologous CiaR-controlled Ccn sRNAs of Streptococcus pneumoniae modulate Zn-resistance.

Nicholas R De Lay, Nidhi Verma, Dhriti Sinha, Abigail Garrett, Maximillian K Osterberg, Daisy Porter, Spencer Reiling, David P Giedroc, Malcolm E Winkler

Abstract read
In one paragraph

Article in PLoS pathogens, 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
–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

2 citing papers in PubMed.

  1. Transcriptomic analysis ofMicrobial genomics · 2025
    Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Nicholas R De LayDepartment of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center, Houston, Texas, United States of America.ORCID 0000-0003-2249-7073
Nidhi VermaDepartment of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center, Houston, Texas, United States of America.
Dhriti SinhaDepartment of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center, Houston, Texas, United States of America.
Abigail GarrettDepartment of Biology, Indiana University Bloomington, Bloomington, Indiana, United States of America.
Maximillian K OsterbergDepartment of Chemistry, Indiana University, Bloomington, Bloomington, Indiana, United States of America.
Daisy PorterDepartment of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center, Houston, Texas, United States of America.
Spencer ReilingDepartment of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center, Houston, Texas, United States of America.
David P GiedrocDepartment of Chemistry, Indiana University, Bloomington, Bloomington, Indiana, United States of America.
Malcolm E WinklerDepartment of Biology, Indiana University Bloomington, Bloomington, Indiana, United States of America.

Funding

Transition Metal Homeostasis and Reactive Sulfur Species in Bacterial PathogensR35GM118157 · NIGMS · TRUSTEES OF INDIANA UNIVERSITY · PI DAVID P. GIEDROC · 2016 to 2026
$5.9M
New Regulatory Interactions and Circuits that Mediate the Dynamics, Homeostasis, and Stress Responses of Peptidoglycan Synthesis in the Superbug Streptococcus pneumoniaeR35GM131767 · NIGMS · TRUSTEES OF INDIANA UNIVERSITY · PI MALCOLM E. WINKLER · 2019 to 2026
$4.8M
Graduate Training Program in Quantitative and Chemical Biology at Indiana University BloomingtonT32GM131994 · NIGMS · TRUSTEES OF INDIANA UNIVERSITY · PI JARED C LEWIS · 2019 to 2026
$2.4M
Small RNA based control of zinc homeostasis in Streptococcus pneumoniaeR21AI171771 · NIAID · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI DE LAY, NICHOLAS R. · 2022 to 2023
$429k
NIAID NIH HHS R21 AI171771NIGMS NIH HHS R35 GM118157NIGMS NIH HHS R35 GM131767NIGMS NIH HHS T32 GM131994
6 · The paper itself

Abstract

Zinc is a vital transition metal for all bacteria; however, elevated intracellular free Zn levels can result in mis-metalation of Mn-dependent enzymes. For Mn-centric bacteria such as Streptococcus pneumoniae that primarily use Mn instead of Fe as an enzyme cofactor, Zn is particularly toxic at high concentrations. Here, we report our identification and characterization of the function of the five homologous, CiaRH-regulated Ccn sRNAs in controlling S. pneumoniae virulence and metal homeostasis. We show that deletion of all five ccn genes (ccnA, ccnB, ccnC, ccnD, and ccnE) from S. pneumoniae strains D39 (serotype 2) and TIGR4 (serotype 4) causes Zn hypersensitivity and an attenuation of virulence in a murine invasive pneumonia model. We provide evidence that bioavailable Zn disproportionately increases in S. pneumoniae strains lacking the five ccn genes. Consistent with a response to Zn intoxication or relatively high intracellular free Zn levels, expression of genes encoding the CzcD Zn exporter and the Mn-independent ribonucleotide reductase, NrdD-NrdG, were increased in the ΔccnABCDE mutant relative to its isogenic ccn+ parent strain. The growth inhibition by Zn that occurs as the result of loss of the ccn genes is rescued by supplementation with Mn or Oxyrase, a reagent that removes dissolved oxygen. Lastly, we found that the Zn-dependent growth inhibition of the ΔccnABCDE strain was not altered by deletion of sodA, whereas the ccn+ ΔsodA strain phenocopied the ΔccnABCDE strain. Overall, our results indicate that the Ccn sRNAs have a crucial role in preventing Zn intoxication in S. pneumoniae.

Indexed as

Streptococcus pneumoniaeZincAnimalsBacterial ProteinsFemaleGene Expression Regulation, BacterialMiceRNA, BacterialVirulenceBacterial ProteinsRNA, BacterialZinc

Identifiers

PMID39361718
PMCPMC11478796

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.