Evidence map›Paper›PMID 26572616›Full record

ArticleBMC microbiology2015

Nontypeable Haemophilus influenzae exploits the interaction between protein-E and vitronectin for the adherence and invasion to bronchial epithelial cells.

Masaki Ikeda, Noriyuki Enomoto, Dai Hashimoto, Tomoyuki Fujisawa, Naoki Inui, Yutaro Nakamura, Takafumi Suda, Toshi Nagata

Open access · goldAbstract read
In one paragraph

Article in BMC microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 26 citations in OpenAlex.

  1. Exploiting haem-iron dependence of nontypeableFrontiers in cellular and infection microbiology · 2025
    Review
  2. Review
  3. Persistent microbial infections and idiopathic pulmonary fibrosis - an insight intoFrontiers in cellular and infection microbiology · 2024
    Review
  4. Article
  5. Haemophilin-Producing Strains ofPathogens (Basel, Switzerland) · 2021
    Article
  6. Panel 7 - Pathogenesis of otitis media - a review of the literature between 2015 and 2019.International journal of pediatric otorhinolaryngology · 2020
    Review
  7. Review
  8. The Contribution of Geogenic Particulate Matter to Lung Disease in Indigenous Children.International journal of environmental research and public health · 2019
    Article
  9. Article
  10. How bacteria hack the matrix and dodge the bullets of immunity.European respiratory review : an official journal of the European Respiratory Society · 2018
    Review
  11. Article
  12. Review
  13. Antimicrobial Peptides SLPI and Beta Defensin-1 in Sputum are Negatively Correlated with FEVInternational journal of chronic obstructive pulmonary disease
    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

8 authors at 1 institution in 1 country.

Masaki IkedaSecond Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. ike-masa@hama-med.ac.jp.
Noriyuki EnomotoSecond Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. norieno@hama-med.ac.jp.
Dai HashimotoSecond Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. dai.hashimoto0915@gmail.com.
Tomoyuki FujisawaSecond Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. fujisawa@hama-med.ac.jp.
Naoki InuiDepartment of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan. inui@hama-med.ac.jp.
Yutaro NakamuraSecond Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. nakayuta@hama-med.ac.jp.
Takafumi SudaSecond Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. suda@hama-med.ac.jp.
Toshi NagataDepartment of Health Science, Hamamatsu University School of Medicine, Hamamatsu, Japan. tnagata@hama-med.ac.jp.
Hamamatsu University School of Medicine · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNontypeable Haemophilus influenzae (NTHi) is one of the most common Gram-negative pathogens in otitis media and exacerbation of chronic obstructive pulmonary disease. NTHi has been reported to invade bronchial epithelial cells. This penetration enables NTHi to evade the host immune system and antibiotics, and it seems to be related to the intractable features of these diseases. However, the precise mechanism of the invasion has been unknown. We hypothesized that protein-E, an outer membrane protein of NTHi, plays a role in this penetration into bronchial epithelial cells.

resultsWe utilized two NTHi strains. NTHi efficiently attached to plate-bound vitronectin (254-309/field at 1,000× magnification) and this attachment was blocked by pretreatment with protein-E peptide (PE84-108). The blockade of adhesion was dependent on the concentration of PE84-108. NTHi strains invaded bronchial epithelial cells and the intracellular bacteria were localized in early endosomes. Furthermore, intracellular invasion of NTHi was also blocked by PE84-108, but not by Arg-Gly-Asp (RGD) peptide. Pretreatment with PE84-108 significantly prevented cells from being invaded by both NTHi strains, which was confirmed by fluorescent microscope observation. In addition, pretreatment with PE84-108 significantly reduced percentages of CFU after gentamicin treatment of cells per input CFU.

conclusionsThese results suggest that NTHi does not directly bind to the cell surface, but binds to host vitronectin that is bound to the cell surface, via bacterial protein-E. Bacterial protein-E and host vitronectin play a role in the attachment to bronchial epithelial cells and is also involved in the subsequent intracellular invasion of NTHi. A novel vaccine or treatment strategy targeting the protein-E-vitronectin axis may prevent respiratory intracellular infection of NTHi and may lead to better clinical outcomes.

Indexed as

Bacterial AdhesionEndocytosisHost-Pathogen InteractionsBacterial Outer Membrane ProteinsEpithelial CellsHaemophilus influenzaeHumansProtein BindingVitronectinBacterial Outer Membrane ProteinsVitronectin

Identifiers

PMID26572616
PMCPMC4647820
OpenAlexW2218578361

What OpenQuestion holds

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LicenceCC BY
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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.