Evidence map›Paper›PMID 27068095›Full record

ArticleInfection and immunity2016

The Clostridium difficile Dlt Pathway Is Controlled by the Extracytoplasmic Function Sigma Factor σV in Response to Lysozyme.

Emily C Woods, Kathryn L Nawrocki, Jose M Suárez, Shonna M McBride

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

32 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
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  3. Identification of DraRS inJournal of bacteriology · 2023
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  9. Activation of the extracytoplasmic function σ factor σCurrent opinion in microbiology · 2022
    Review
  10. Article
  11. Article
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  16. Review
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  19. Article
  20. Regulation and Anaerobic Function of theAntimicrobial agents and chemotherapy · 2019
    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.

Emily C WoodsDepartment of Microbiology and Immunology, Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, Georgia, USA.
Kathryn L NawrockiDepartment of Microbiology and Immunology, Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, Georgia, USA.
Jose M SuárezDepartment of Microbiology and Immunology, Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, Georgia, USA.
Shonna M McBrideDepartment of Microbiology and Immunology, Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, Georgia, USA shonna.mcbride@emory.edu.
Emory University · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM008169 · NIGMS · EMORY UNIVERSITY · PI GROSS, ROBERT E · 1987 to 2021
$20.3M
Host-induced Initiation of Clostridium difficile SporulationR01AI116933 · NIAID · EMORY UNIVERSITY · PI SHONNA M. MCBRIDE · 2015 to 2026
$4.8M
Antimicrobial Resistance and Therapeutic Discovery Training ProgramT32AI106699 · NIAID · EMORY UNIVERSITY · PI Graeme L Conn, Joanna B Goldberg · 2014 to 2026
$2.7M
Molecular Mechanisms of Clostridium difficile Resistance to Innate Host DefensesK01DK087763 · NIDDK · TUFTS UNIVERSITY BOSTON · PI MCBRIDE, SHONNA M. · 2011 to 2015
$713k
Regulation of Clostridium difficile Spore FormationR56AI109526 · NIAID · EMORY UNIVERSITY · PI MCBRIDE, SHONNA M. · 2014 to 2014
$383k
Role of Antimicrobial Resistance in Epidemic Clostridium difficile InfectionsR03DK101870 · NIDDK · EMORY UNIVERSITY · PI MCBRIDE, SHONNA M. · 2014 to 2015
$156k
NIAID NIH HHS R01 AI116933NIAID NIH HHS R56 AI109526NIAID NIH HHS T32 AI106699NIDDK NIH HHS K01 DK087763NIDDK NIH HHS R03 DK101870NIGMS NIH HHS T32 GM008169
6 · The paper itself

Abstract

Clostridium difficile (also known as Peptoclostridium difficile) is a major nosocomial pathogen and a leading cause of antibiotic-associated diarrhea throughout the world. Colonization of the intestinal tract is necessary for C. difficile to cause disease. Host-produced antimicrobial proteins (AMPs), such as lysozyme, are present in the intestinal tract and can deter colonization by many bacterial pathogens, and yet C. difficile is able to survive in the colon in the presence of these AMPs. Our prior studies established that the Dlt pathway, which increases the surface charge of the bacterium by addition of d-alanine to teichoic acids, is important for C. difficile resistance to a variety of AMPs. We sought to determine what genetic mechanisms regulate expression of the Dlt pathway. In this study, we show that a dlt null mutant is severely attenuated for growth in lysozyme and that expression of the dltDABC operon is induced in response to lysozyme. Moreover, we found that a mutant lacking the extracytoplasmic function (ECF) sigma factor σ(V) does not induce dlt expression in response to lysozyme, indicating that σ(V) is required for regulation of lysozyme-dependent d-alanylation of the cell wall. Using reporter gene fusions and 5' RACE (rapid amplification of cDNA ends) analysis, we identified promoter elements necessary for lysozyme-dependent and lysozyme-independent dlt expression. In addition, we observed that both a sigV mutant and a dlt mutant are more virulent in a hamster model of infection. These findings demonstrate that cell wall d-alanylation in C. difficile is induced by lysozyme in a σ(V)-dependent manner and that this pathway impacts virulence in vivo.

Indexed as

Gene Expression Regulation, BacterialHost-Pathogen InteractionsAlanineAnimalsBacterial ProteinsCarrier ProteinsCell WallClostridioides difficileCricetulusDisease Models, AnimalEnterocolitis, PseudomembranousFemaleMuramidaseMutationOperonPromoter Regions, GeneticAlanineBacterial ProteinsCarrier ProteinsD-alanyl carrier protein, bacteriaMuramidaseProtein IsoformsSigma FactorTeichoic Acids

Identifiers

PMID27068095
PMCPMC4907151
OpenAlexW2395698339

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.