Evidence map›Paper›PMID 22988021›Full record

ArticleInfection and immunity2012

Cyclic di-GMP stimulates biofilm formation and inhibits virulence of Francisella novicida.

Xhavit Zogaj, Geoff C Wyatt, Karl E Klose

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2012. 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
1.7field-weighted citation impact, top 16% 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, 36 citations in OpenAlex.

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  11. Genetic Determinants of Antibiotic Resistance inFrontiers in microbiology · 2021
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  12. Review
  13. Control ofMicroorganisms · 2020
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  17. Innate Immune Recognition: An Issue More Complex Than Expected.Frontiers in cellular and infection microbiology · 2019
    Review
  18. Article
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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 2 institutions in 1 country.

Xhavit ZogajSouth Texas Center for Emerging Infectious Diseases and Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA.
Geoff C Wyatt
Karl E Klose
The University of Texas at San Antonio · USTexas Center for Infectious Disease · US

Funding

Tularemia: Pathogenesis and Host ResponseP01AI057986 · NIAID · UNIVERSITY OF TEXAS SAN ANTONIO · PI KLOSE, KARL E · 2005 to 2009
$6.1M
NIAID NIH HHS P01 AI057986NIAID NIH HHS P01 AI57986
6 · The paper itself

Abstract

Francisella tularensis is a gram-negative bacterium that is highly virulent in humans, causing the disease tularemia. F. novicida is closely related to F. tularensis and exhibits high virulence in mice, but it is avirulent in healthy humans. An F. novicida-specific gene cluster (FTN0451 to FTN0456) encodes two proteins with diguanylate cyclase (DGC) and phosphodiesterase (PDE) domains that modulate the synthesis and degradation of cyclic di-GMP (cdGMP). No DGC- or PDE-encoding protein genes are present in the F. tularensis genome. F. novicida strains lacking either the two DGC/PDE genes (cdgA and cdgB) or the entire gene cluster (strain KKF457) are defective for biofilm formation. In addition, expression of CdgB or a heterologous DGC in strain KKF457 stimulated F. novicida biofilms, even in a strain lacking the biofilm regulator QseB. Genetic evidence suggests that CdgA is predominantly a PDE, while CdgB is predominantly a DGC. The F. novicida qseB strain showed reduced cdgA and cdgB transcript levels, demonstrating an F. novicida biofilm signaling cascade that controls cdGMP levels. Interestingly, KKF457 with elevated cdGMP levels exhibited a decrease in intramacrophage replication and virulence in mice, as well as increased growth yields and biofilm formation in vitro. Microarray analyses revealed that cdGMP stimulated the transcription of a chitinase (ChiB) known to contribute to biofilm formation. Our results indicate that elevated cdGMP in F. novicida stimulates biofilm formation and inhibits virulence. We suggest that differences in human virulence between F. novicida and F. tularensis may be due in part to the absence of cdGMP signaling in F. tularensis.

Indexed as

AnimalsBacterial ProteinsBiofilmsChitinasesCyclic GMPFemaleFrancisellaGene Expression Regulation, BacterialGram-Negative Bacterial InfectionsHumansMiceMice, Inbred BALB CMolecular Sequence DataOligonucleotide Array Sequence AnalysisSequence Analysis, DNAVirulenceBacterial Proteinsbis(3',5')-cyclic diguanylic acidChitinasesCyclic GMP

Identifiers

PMID22988021
PMCPMC3497427
OpenAlexW2043968316

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.