Evidence map›Paper›PMID 27176600›Full record

ArticleBMC microbiology2016

Target identification in Fusobacterium nucleatum by subtractive genomics approach and enrichment analysis of host-pathogen protein-protein interactions.

Amit Kumar, Pragna Lakshmi Thotakura, Basant Kumar Tiwary, Ramadas Krishna

Open access · goldAbstract read
In one paragraph

Article in BMC microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% 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

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

  1. World journal of gastroenterology · 2017
    Pooled it
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  3. Review
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  10. Screening of Novel Drug Targets and Drug Design forCurrent research in microbial sciences · 2024
    Article
  11. Review
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  13. Journal of oral microbiology · 2023
    Review
  14. Article
  15. Article
  16. In Silico Core Proteomics and Molecular Docking Approaches for the Identification of Novel Inhibitors againstInternational journal of environmental research and public health · 2021
    Article
  17. Article
  18. Review
  19. Review
  20. 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.

Amit KumarCentre for Bioinformatics, Pondicherry University, Puducherry, 605014, India.
Pragna Lakshmi ThotakuraCentre for Bioinformatics, Pondicherry University, Puducherry, 605014, India.
Basant Kumar TiwaryCentre Head, Centre for Bioinformatics, Pondicherry University, Puducherry, 605014, India.
Ramadas KrishnaCentre for Bioinformatics, Pondicherry University, Puducherry, 605014, India. krishstrucbio@gmail.com.
Pondicherry University · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFusobacterium nucleatum, a well studied bacterium in periodontal diseases, appendicitis, gingivitis, osteomyelitis and pregnancy complications has recently gained attention due to its association with colorectal cancer (CRC) progression. Treatment with berberine was shown to reverse F. nucleatum-induced CRC progression in mice by balancing the growth of opportunistic pathogens in tumor microenvironment. Intestinal microbiota imbalance and the infections caused by F. nucleatum might be regulated by therapeutic intervention. Hence, we aimed to predict drug target proteins in F. nucleatum, through subtractive genomics approach and host-pathogen protein-protein interactions (HP-PPIs). We also carried out enrichment analysis of host interacting partners to hypothesize the possible mechanisms involved in CRC progression due to F. nucleatum.

resultsIn subtractive genomics approach, the essential, virulence and resistance related proteins were retrieved from RefSeq proteome of F. nucleatum by searching against Database of Essential Genes (DEG), Virulence Factor Database (VFDB) and Antibiotic Resistance Gene-ANNOTation (ARG-ANNOT) tool respectively. A subsequent hierarchical screening to identify non-human homologous, metabolic pathway-independent/pathway-specific and druggable proteins resulted in eight pathway-independent and 27 pathway-specific druggable targets. Co-aggregation of F. nucleatum with host induces proinflammatory gene expression thereby potentiates tumorigenesis. Hence, proteins from IBDsite, a database for inflammatory bowel disease (IBD) research and those involved in colorectal adenocarcinoma as interpreted from The Cancer Genome Atlas (TCGA) were retrieved to predict drug targets based on HP-PPIs with F. nucleatum proteome. Prediction of HP-PPIs exhibited 186 interactions contributed by 103 host and 76 bacterial proteins. Bacterial interacting partners were accounted as putative targets. And enrichment analysis of host interacting partners showed statistically enriched terms that were in positive correlation with CRC, atherosclerosis, cardiovascular, osteoporosis, Alzheimer's and other diseases.

conclusionSubtractive genomics analysis provided a set of target proteins suggested to be indispensable for survival and pathogenicity of F. nucleatum. These target proteins might be considered for designing potent inhibitors to abrogate F. nucleatum infections. From enrichment analysis, it was hypothesized that F. nucleatum infection might enhance CRC progression by simultaneously regulating multiple signaling cascades which could lead to up-regulation of proinflammatory responses, oncogenes, modulation of host immune defense mechanism and suppression of DNA repair system.

Indexed as

Protein Interaction MappingAnimalsDatabases, GeneticDrug Resistance, BacterialFusobacterium nucleatumGene OntologyGenes, EssentialGenomicsHost-Pathogen InteractionsHumansVirulenceColorectal cancerDAVIDEnrichment analysisFunctional annotationFusobacterium nucleatumGene ontologyHost-pathogen protein-protein interactionsPathway and disease enrichmentSubtractive genomics approachTherapeutic target proteins

Identifiers

PMID27176600
PMCPMC4866016
OpenAlexW2394170340

What OpenQuestion holds

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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.