Evidence map›Paper›PMID 25633080›Full record

ArticlePLoS pathogens2015

Elucidation of the RamA regulon in Klebsiella pneumoniae reveals a role in LPS regulation.

Shyamasree De Majumdar, Jing Yu, Maria Fookes, Sean P McAteer, Enrique Llobet, Sarah Finn, Shaun Spence, Avril Monahan, Avril Monaghan, Adrien Kissenpfennig and 6 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

83 citing papers in PubMed, 160 citations in OpenAlex.

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  16. Emergence of concurrently transmissibleMicrobiology spectrum · 2025
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  18. Mechanisms of Antimicrobial Resistance inInfection and drug resistance · 2025
    Review
  19. Article
  20. Review

23 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 6 institutions in 2 countries.

Shyamasree De MajumdarCentre for Infection and Immunity, Belfast, United Kingdom; Division of Pathway and Infection Medicine, Edinburgh, United Kingdom.
Jing YuCentre for Infection and Immunity, Belfast, United Kingdom.
Maria FookesWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
Sean P McAteerDivision of Immunity and Infection, The Roslin Institute and R(D)SVS, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom.
Enrique LlobetLaboratory Microbial Pathogenesis, Fundació d'Investigació Sanitària de les Illes Balears (FISIB) Recinto Hospital Joan March, Bunyola, Spain.
Sarah FinnUCD Centre for Molecular Innovation and Drug Discovery, School of Public Health, Physiotherapy & Population Science, University College Dublin, Dublin, Ireland.
Shaun SpenceCentre for Infection and Immunity, Belfast, United Kingdom.
Avril Monahan
Avril MonaghanCentre for Infection and Immunity, Belfast, United Kingdom.
Adrien KissenpfennigCentre for Infection and Immunity, Belfast, United Kingdom.
Rebecca J IngramCentre for Infection and Immunity, Belfast, United Kingdom.
José BengoecheaCentre for Infection and Immunity, Belfast, United Kingdom; Laboratory Microbial Pathogenesis, Fundació d'Investigació Sanitària de les Illes Balears (FISIB) Recinto Hospital Joan March, Bunyola, Spain.
David L GallyDivision of Immunity and Infection, The Roslin Institute and R(D)SVS, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom.
Séamus FanningUCD Centre for Molecular Innovation and Drug Discovery, School of Public Health, Physiotherapy & Population Science, University College Dublin, Dublin, Ireland.
Joseph S ElbornCentre for Infection and Immunity, Belfast, United Kingdom.
Thamarai SchneidersCentre for Infection and Immunity, Belfast, United Kingdom; Division of Pathway and Infection Medicine, Edinburgh, United Kingdom.
Centre for Immunity, Infection and Evolution · GBInfection Prevention Society · GBUniversity College Dublin · IERoslin Institute · GBUniversity of Edinburgh · GBWellcome Sanger Institute · GB

Funding

Biotechnology and Biological Sciences Research CouncilMedical Research Council G0601199Wellcome TrustWellcome Trust 098051
6 · The paper itself

Abstract

Klebsiella pneumoniae is a significant human pathogen, in part due to high rates of multidrug resistance. RamA is an intrinsic regulator in K. pneumoniae established to be important for the bacterial response to antimicrobial challenge; however, little is known about its possible wider regulatory role in this organism during infection. In this work, we demonstrate that RamA is a global transcriptional regulator that significantly perturbs the transcriptional landscape of K. pneumoniae, resulting in altered microbe-drug or microbe-host response. This is largely due to the direct regulation of 68 genes associated with a myriad of cellular functions. Importantly, RamA directly binds and activates the lpxC, lpxL-2 and lpxO genes associated with lipid A biosynthesis, thus resulting in modifications within the lipid A moiety of the lipopolysaccharide. RamA-mediated alterations decrease susceptibility to colistin E, polymyxin B and human cationic antimicrobial peptide LL-37. Increased RamA levels reduce K. pneumoniae adhesion and uptake into macrophages, which is supported by in vivo infection studies, that demonstrate increased systemic dissemination of ramA overexpressing K. pneumoniae. These data establish that RamA-mediated regulation directly perturbs microbial surface properties, including lipid A biosynthesis, which facilitate evasion from the innate host response. This highlights RamA as a global regulator that confers pathoadaptive phenotypes with implications for our understanding of the pathogenesis of Enterobacter, Salmonella and Citrobacter spp. that express orthologous RamA proteins.

Indexed as

AnimalsAnti-Bacterial AgentsAntimicrobial Cationic PeptidesBacterial ProteinsBase SequenceCells, CulturedDrug Resistance, Multiple, BacterialGene Expression Regulation, BacterialGenes, BacterialHost-Pathogen InteractionsKlebsiella InfectionsKlebsiella pneumoniaeLipopolysaccharidesMembrane Transport ProteinsMiceMice, Inbred C57BLAnti-Bacterial AgentsAntimicrobial Cationic PeptidesBacterial ProteinsLipopolysaccharidesMembrane Transport ProteinsPolymyxinsRamA protein, Klebsiella

Identifiers

PMID25633080
PMCPMC4310594
OpenAlexW2097910397

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.