Evidence map›Paper›PMID 19687228›Full record

ArticleThe Journal of experimental medicine2009

The surface-anchored NanA protein promotes pneumococcal brain endothelial cell invasion.

Satoshi Uchiyama, Aaron F Carlin, Arya Khosravi, Shannon Weiman, Anirban Banerjee, Darin Quach, George Hightower, Tim J Mitchell, Kelly S Doran, Victor Nizet

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.

0numbers the graph read from it
0cells of the map it votes in
108citing papers in PubMed
10.3field-weighted citation impact, top 1% 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

108 citing papers in PubMed, 179 citations in OpenAlex.

  1. Review
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  12. Understanding the mechanisms ofTissue barriers · 2025
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  17. Bacterial meningitis in Africa.Frontiers in neurology · 2023
    Review
  18. Role ofFrontiers in cellular and infection microbiology · 2023
    Review
  19. Review
  20. Article

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

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

10 authors at 3 institutions in 2 countries.

Satoshi UchiyamaDepartment of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
Aaron F Carlin
Arya Khosravi
Shannon Weiman
Anirban Banerjee
Darin Quach
George Hightower
Tim J Mitchell
Kelly S Doran
Victor Nizet
University of California San Diego · USSan Diego State University · USUniversity of Glasgow · GB

Funding

GRADUATE TRAINING IN CELLULAR &MOLECULAR PHARMACOLOGYT32GM007752 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER, HANDEL, TRACY M · 1985 to 2023
$13.5M
GAS Switch from Colonizing Bacterium to Invasive PathogenR01AI077780 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NIZET, VICTOR · 2008 to 2019
$3.8M
Blood-brain barrier in bacterial meningitisR01NS051247 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DORAN, KELLY S · 2006 to 2015
$3.2M
Sialic Acid O-Acetylation in GBS Pathogenesis & ImmunityR01HD051796 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NIZET, VICTOR · 2006 to 2010
$1.6M
Blood Brain Barrier Failure in Bacterial MeningitisR56NS051247 · NINDS · UNIVERSITY OF COLORADO DENVER · PI DORAN, KELLY S · 2016 to 2018
$765k
Medical Research CouncilNIAID NIH HHS AI077780NIAID NIH HHS R01 AI077780NICHD NIH HHS HD051796NICHD NIH HHS R01 HD051796NIGMS NIH HHS T32 GM007752NINDS NIH HHS NS051247NINDS NIH HHS R01 NS051247Wellcome Trust
6 · The paper itself

Abstract

In humans, Streptococcus pneumoniae (SPN) is the leading cause of bacterial meningitis, a disease with high attributable mortality and frequent permanent neurological sequelae. The molecular mechanisms underlying the central nervous system tropism of SPN are incompletely understood, but include a primary interaction of the pathogen with the blood-brain barrier (BBB) endothelium. All SPN strains possess a gene encoding the surface-anchored sialidase (neuraminidase) NanA, which cleaves sialic acid on host cells and proteins. Here, we use an isogenic SPN NanA-deficient mutant and heterologous expression of the protein to show that NanA is both necessary and sufficient to promote SPN adherence to and invasion of human brain microvascular endothelial cells (hBMECs). NanA-mediated hBMEC invasion depends only partially on sialidase activity, whereas the N-terminal lectinlike domain of the protein plays a critical role. NanA promotes SPN-BBB interaction in a murine infection model, identifying the protein as proximal mediator of CNS entry by the pathogen.

Indexed as

AnimalsBlood-Brain BarrierCell AdhesionDNA PrimersEndothelial CellsHumansMaleMeningitis, BacterialMiceMice, Inbred BALB CN-Acetylneuraminic AcidNeuraminidasePlasmidsStreptococcus pneumoniae2-deoxy-2,3-dehydro-N-acetylneuraminic acidDNA PrimersN-Acetylneuraminic AcidNeuraminidase

Identifiers

PMID19687228
PMCPMC2737157
OpenAlexW2111965293

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.