Evidence map›Paper›PMID 24003154›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Genome-wide fitness profiling reveals adaptations required by Haemophilus in coinfection with influenza A virus in the murine lung.

Sandy M Wong, Mariana Bernui, Hao Shen, Brian J Akerley

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

39 citing papers in PubMed, 55 citations in OpenAlex.

  1. Review
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  11. Learning from -omics strategies applied to uncoverComputational and structural biotechnology journal · 2021
    Review
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  13. Viruses · 2020
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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

4 authors at 2 institutions in 1 country.

Sandy M WongDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605.
Mariana Bernui
Hao Shen
Brian J Akerley
University of Massachusetts Chan Medical School · USUniversity of Pennsylvania · US

Funding

The Impact of Bacterial Co-Infectin on Respiratory Virus-Specific T cell ResponseU19AI083022 · NIAID · WISTAR INSTITUTE · PI WHERRY, E. JOHN · 2009 to 2013
$10.7M
Global regulatory interactions in bacterial pathogenesisR01AI049437 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI AKERLEY, BRIAN J. · 2002 to 2006
$1.9M
Mechanisms of Haemophilus influenzae pathogenesis in the lungR01AI095740 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI AKERLEY, BRIAN, SHEN, HAO · 2012 to 2016
$1.8M
Mechanisms of Haemophilus influenzae pathogenesis in the lungR56AI095740 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI AKERLEY, BRIAN, SHEN, HAO · 2011 to 2011
$424k
Global regulatory interactions in bacterial pathogenesisR56AI049437 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI AKERLEY, BRIAN · 2009 to 2009
$410k
NIAID NIH HHS R01 AI049437NIAID NIH HHS R01 AI095740NIAID NIH HHS R01AI095740NIAID NIH HHS R56 AI049437NIAID NIH HHS R56AI049437NIAID NIH HHS R56 AI095740NIAID NIH HHS U19 AI083022NIAID NIH HHS U19AI083022
6 · The paper itself

Abstract

Bacterial coinfection represents a major cause of morbidity and mortality in epidemics of influenza A virus (IAV). The bacterium Haemophilus influenzae typically colonizes the human upper respiratory tract without causing disease, and yet in individuals infected with IAV, it can cause debilitating or lethal secondary pneumonia. Studies in murine models have detected immune components involved in susceptibility and pathology, and yet few studies have examined bacterial factors contributing to coinfection. We conducted genome-wide profiling of the H. influenzae genes that promote its fitness in a murine model of coinfection with IAV. Application of direct, high-throughput sequencing of transposon insertion sites revealed fitness phenotypes of a bank of H. influenzae mutants in viral coinfection in comparison with bacterial infection alone. One set of virulence genes was required in nonvirally infected mice but not in coinfection, consistent with a defect in anti-bacterial defenses during coinfection. Nevertheless, a core set of genes required in both in vivo conditions indicated that many bacterial countermeasures against host defenses remain critical for coinfection. The results also revealed a subset of genes required in coinfection but not in bacterial infection alone, including the iron-sulfur cluster regulator gene, iscR, which was required for oxidative stress resistance. Overexpression of the antioxidant protein Dps in the iscR mutant restored oxidative stress resistance and ability to colonize in coinfection. The results identify bacterial stress and metabolic adaptations required in an IAV coinfection model, revealing potential targets for treatment or prevention of secondary bacterial pneumonia after viral infection.

Indexed as

Adaptation, BiologicalAnimalsCoinfectionDNA Transposable ElementsGenetic FitnessHaemophilusHaemophilus InfectionsHigh-Throughput Nucleotide SequencingInfluenza A virusLungMiceOrthomyxoviridae InfectionsReverse Transcriptase Polymerase Chain ReactionTranscription FactorsDNA Transposable ElementsTranscription Factorsfunctional genomicstransposon-insertion sequencing

Identifiers

PMID24003154
PMCPMC3780910
OpenAlexW2106527072

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.