Evidence map›Paper›PMID 22451523›Full record

ArticleInfection and immunity2012

Functional differences and interactions between the Escherichia coli type III secretion system effectors NleH1 and NleH2.

Thanh H Pham, Xiaofei Gao, Karen Tsai, Rachel Olsen, Fengyi Wan, Philip R Hardwidge

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

28 citing papers in PubMed, 54 citations in OpenAlex.

  1. Article
  2. Cell Death and Infection: Implications for Host and Microbe.Advances in experimental medicine and biology · 2025
    Review
  3. Article
  4. Targeting of microvillus protein Eps8 by the NleH effector kinases from enteropathogenicProceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  5. Review
  6. Review
  7. Article
  8. Hsp90 Interacts with the Bacterial Effector NleH1.Pathogens (Basel, Switzerland) · 2018
    Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Review
  20. Review
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

6 authors at 2 institutions in 1 country.

Thanh H PhamDepartment of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA.
Xiaofei Gao
Karen Tsai
Rachel Olsen
Fengyi Wan
Philip R Hardwidge
University of Kansas Medical Center · USJohns Hopkins University · US

Funding

Novel Subunit of NF-kB Confers Gene Regulatory SpecificityR00CA137171 · NCI · JOHNS HOPKINS UNIVERSITY · PI WAN, FENGYI · 2011 to 2013
$710k
Disruption of NF-kB signaling by diarrheagenic Escherichia coliR56AI087686 · NIAID · UNIVERSITY OF KANSAS MEDICAL CENTER · PI HARDWIDGE, PHILIP ROSS · 2010 to 2010
$370k
Host subversion by E. coli O157:H7 effector proteinsR03AI076227 · NIAID · UNIVERSITY OF KANSAS MEDICAL CENTER · PI HARDWIDGE, PHILIP ROSS · 2009 to 2010
$149k
NCI NIH HHS CA137171NCI NIH HHS K99 CA137171NCI NIH HHS R00 CA137171NIAID NIH HHS AI076227NIAID NIH HHS AI087686NIAID NIH HHS R03 AI076227NIAID NIH HHS R56 AI087686
6 · The paper itself

Abstract

The human pathogens enterohemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC), as well as the related mouse pathogen Citrobacter rodentium, utilize a type III secretion system (T3SS) to inject multiple effector proteins into host cells. The E. coli O157:H7 strain EDL933 carries two copies of non-locus of enterocyte effacement (LEE)-encoded protein H, designated NleH1 and NleH2, both of which bind to the human ribosomal protein S3 (RPS3), a subunit of NF-κB transcriptional complexes. In this study, we describe significant functional differences between NleH1 and NleH2 in their ability to regulate the host NF-κB pathway. We show that the EHEC and EPEC NleH effectors are functionally equivalent in their ability to affect RPS3 nuclear translocation. NleH1, but not NleH2, inhibited NF-κB activity without altering the kinetics of IκBα phosphorylation/degradation. We also determined that the class I PSD-95/Disc Large/ZO-1 (PDZ)-binding domain of NleH was important for its activity in the NF-κB pathway. In addition to binding RPS3, we found that NleH1 and NleH2 are able to bind to each other in vitro and in vivo, suggesting an additional mechanism by which the E. coli NleH effectors may regulate the extent and duration of NF-κB activation after their T3SS-dependent translocation. We also performed mouse infection experiments and established that mouse mortality and Citrobacter colonization were reduced in mice infected with ΔnleH. Complementing ΔnleH with NleH1 restored Citrobacter virulence and colonization to wild-type levels, whereas complementing with NleH2 reduced them. Taken together, our data show that NleH1 and NleH2 have pronounced functional differences in their ability to alter host transcriptional responses to bacterial infection.

Indexed as

AnimalsCitrobacter rodentiumEnterobacteriaceae InfectionsEscherichia coli O157Escherichia coli ProteinsGene Expression Regulation, BacterialHEK293 CellsHeLa CellsHumansMiceMice, Inbred C3HMice, Inbred C57BLMutationNF-kappa BProtein BindingReverse Transcriptase Polymerase Chain ReactionEscherichia coli ProteinsNF-kappa BNleH protein, E coliRibosomal Proteinsribosomal protein S3

Identifiers

PMID22451523
PMCPMC3370600
OpenAlexW2092627831

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.