Evidence map›Paper›PMID 18369477›Full record

ArticlePLoS pathogens2008

RNAi screen reveals an Abl kinase-dependent host cell pathway involved in Pseudomonas aeruginosa internalization.

Julia F Pielage, Kimberly R Powell, Daniel Kalman, Joanne N Engel

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

41 citing papers in PubMed, 76 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Predicting host dependency factors of pathogens inComputational and structural biotechnology journal · 2021
    Article
  6. Review
  7. The Crk adapter protein is essential forMolecular biology of the cell · 2019
    Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. A lipid zipper triggers bacterial invasion.Proceedings of the National Academy of Sciences of the United States of America · 2014
    Article
  17. Review
  18. Assessing Pseudomonas virulence using host cells.Methods in molecular biology (Clifton, N.J.) · 2014
    Article
  19. Article
  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 2 institutions in 1 country.

Julia F PielageProgram in Microbial Pathogenesis and Host Defense, University of California San Francisco, California, USA.
Kimberly R Powell
Daniel Kalman
Joanne N Engel
Emory University · USUniversity of California, San Francisco · US

Funding

MECHANISM OF PSEUDOMONAS MEDIATED EPITHELIAL CELL DAMAGER01AI042806 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ENGEL, JOANNE N. · 1998 to 2010
$4.6M
New approaches to Study Pseudomonas-host interactionsR01AI065902 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ENGEL, JOANNE N. · 2005 to 2013
$2.8M
Role of tyrosine kinases in EPEC and EHEC pathogenesisR01AI056067 · NIAID · EMORY UNIVERSITY · PI KALMAN, DANIEL · 2003 to 2007
$1.6M
New approaches to study Pseudomonas-host interactionsR56AI065902 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ENGEL, JOANNE N. · 2015 to 2015
$396k
NIAID NIH HHS AI056067-01NIAID NIH HHS AI065902NIAID NIH HHS AI42806NIAID NIH HHS R01 AI042806NIAID NIH HHS R01 AI056067NIAID NIH HHS R01 AI065902NIAID NIH HHS R56 AI065902
6 · The paper itself

Abstract

Internalization of the pathogenic bacterium Pseudomonas aeruginosa by non-phagocytic cells is promoted by rearrangements of the actin cytoskeleton, but the host pathways usurped by this bacterium are not clearly understood. We used RNAi-mediated gene inactivation of approximately 80 genes known to regulate the actin cytoskeleton in Drosophila S2 cells to identify host molecules essential for entry of P. aeruginosa. This work revealed Abl tyrosine kinase, the adaptor protein Crk, the small GTPases Rac1 and Cdc42, and p21-activated kinase as components of a host signaling pathway that leads to internalization of P. aeruginosa. Using a variety of complementary approaches, we validated the role of this pathway in mammalian cells. Remarkably, ExoS and ExoT, type III secreted toxins of P. aeruginosa, target this pathway by interfering with GTPase function and, in the case of ExoT, by abrogating P. aeruginosa-induced Abl-dependent Crk phosphorylation. Altogether, this work reveals that P. aeruginosa utilizes the Abl pathway for entering host cells and reveals unexpected complexity by which the P. aeruginosa type III secretion system modulates this internalization pathway. Our results furthermore demonstrate the applicability of using RNAi screens to identify host signaling cascades usurped by microbial pathogens that may be potential targets for novel therapies directed against treatment of antibiotic-resistant infections.

Indexed as

RNA, Small InterferingAdaptor Proteins, Signal TransducingADP Ribose TransferasesAnimalsBacterial ToxinsCell LineCytoskeletonDrosophila melanogasterDrosophila ProteinsGene SilencingGTPase-Activating ProteinsHost-Pathogen InteractionsMacrophagesMiceMice, KnockoutProto-Oncogene Proteins c-ablAdaptor Proteins, Signal TransducingADP Ribose TransferasesBacterial ToxinsDrosophila Proteinsexoenzyme SExoT protein, Pseudomonas aeruginosaGTPase-Activating ProteinsProto-Oncogene Proteins c-ablRNA, Small Interfering

Identifiers

PMID18369477
PMCPMC2265438
OpenAlexW2054278804

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.