Evidence map›Paper›PMID 26351283›Full record

ArticleInfection and immunity2015

Beyond the Crystal Structure: Insight into the Function and Vaccine Potential of TbpA Expressed by Neisseria gonorrhoeae.

Devin R Cash, Nicholas Noinaj, Susan K Buchanan, Cynthia Nau Cornelissen

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

19 citing papers in PubMed, 27 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Article
  5. Clinical microbiology reviews · 2024
    Review
  6. Review
  7. Immune responses toFrontiers in immunology · 2023
    Review
  8. Article
  9. Article
  10. Stealthy microbes: HowFrontiers in cellular and infection microbiology · 2022
    Review
  11. Recent Progress Towards a Gonococcal Vaccine.Frontiers in cellular and infection microbiology · 2022
    Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. 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 3 institutions in 1 country.

Devin R CashDepartment of Microbiology and Immunology, Virginia Commonwealth University, Richmond, Virginia, USA.
Nicholas NoinajLaboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland, USA.
Susan K BuchananLaboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland, USA.
Cynthia Nau CornelissenDepartment of Microbiology and Immunology, Virginia Commonwealth University, Richmond, Virginia, USA cncornel@vcu.edu.
Virginia Commonwealth University · USNational Institute of Diabetes and Digestive and Kidney Diseases · USNational Institutes of Health · US

Funding

Trichomonas Typing SystemU19AI031496 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SPARLING, PHILIP FREDERICK · 1995 to 2014
$24.9M
Structural characterization of outer membrane proteins from Yersinia pestisZIADK011011 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI BUCHANAN, SUSAN · 2009 to 2025
$19.1M
Iron acquisition mechanisms utilized by Neisseria gonorrhoeaeR01AI084400 · NIAID · VIRGINIA COMMONWEALTH UNIVERSITY · PI CORNELISSEN, CYNTHIA N · 2009 to 2010
$674k
Iron acquisition systems in Neisseria gonorrhoeaeR21AI065555 · NIAID · VIRGINIA COMMONWEALTH UNIVERSITY · PI CORNELISSEN, CYNTHIA N · 2006 to 2007
$358k
The role of BamA in the biogenesis of beta-barrel membrane proteinsK22AI113078 · NIAID · PURDUE UNIVERSITY · PI NOINAJ, NICHOLAS · 2015 to 2016
$267k
Neisseria gonorrhoeae TbpA functional analysis and inhibitionF30AI112199 · NIAID · VIRGINIA COMMONWEALTH UNIVERSITY · PI CASH, DEVIN · 2014 to 2017
$134k
Intramural NIH HHSNIAID NIH HHS F30 AI112199NIAID NIH HHS K22 AI113078NIAID NIH HHS R01 AI065555NIAID NIH HHS R01 AI084400NIAID NIH HHS R21 AI065555NIAID NIH HHS U19 AI031496NIAID NIH HHS U19 AI31496
6 · The paper itself

Abstract

Neisseria gonorrhoeae, the causative agent of the sexually transmitted infection gonorrhea, is not preventable by vaccination and is rapidly developing resistance to antibiotics. However, the transferrin (Tf) receptor system, composed of TbpA and TbpB, is an ideal target for novel therapeutics and vaccine development. Using a three-dimensional structure of gonococcal TbpA, we investigated two hypotheses, i.e., that loop-derived antibodies can interrupt ligand-receptor interactions in the native bacterium and that the loop 3 helix is a critical functional domain. Preliminary loop-derived antibodies, as well as optimized second-generation antibodies, demonstrated similar modest ligand-blocking effects on the gonococcal surface but different effects in Escherichia coli. Mutagenesis of loop 3 helix residues was employed, generating 11 mutants. We separately analyzed the mutants' abilities to (i) bind Tf and (ii) internalize Tf-bound iron in the absence of the coreceptor TbpB. Single residue mutations resulted in up to 60% reductions in ligand binding and up to 85% reductions in iron utilization. All strains were capable of growing on Tf as the sole iron source. Interestingly, in the presence of TbpB, only a 30% reduction in Tf-iron utilization was observed, indicating that the coreceptor can compensate for TbpA impairment. Complete deletion of the loop 3 helix of TbpA eliminated the abilities to bind Tf, internalize iron, and grow with Tf as the sole iron source. Our studies demonstrate that while the loop 3 helix is a key functional domain, its function does not exclusively rely on any single residue.

Indexed as

Bacterial ProteinsBacterial VaccinesGonorrheaHumansNeisseria gonorrhoeaeProtein BindingProtein Structure, SecondaryTransferrinTransferrin-Binding Protein ABacterial ProteinsBacterial VaccinesTransferrinTransferrin-Binding Protein A

Identifiers

PMID26351283
PMCPMC4598392
OpenAlexW2336146933

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.