Evidence map›Paper›PMID 19828035›Full record

ArticleBMC microbiology2009

A novel inhibitor of Chlamydophila pneumoniae protein kinase D (PknD) inhibits phosphorylation of CdsD and suppresses bacterial replication.

Dustin L Johnson, Chris B Stone, David C Bulir, Brian K Coombes, James B Mahony

Open access · goldAbstract read
In one paragraph

Article in BMC microbiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.7field-weighted citation impact, top 28% 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

14 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
  2. Type III Secretion inMicrobiology and molecular biology reviews : MMBR · 2023
    Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. The Impact of Protein Phosphorylation on Chlamydial Physiology.Frontiers in cellular and infection microbiology · 2016
    Review
  8. Article
  9. Article
  10. Microbial protein-tyrosine kinases.The Journal of biological chemistry · 2014
    Review
  11. Article
  12. Unity in variety--the pan-genome of the Chlamydiae.Molecular biology and evolution · 2011
    Article
  13. Article
  14. 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

5 authors at 2 institutions in 1 country.

Dustin L JohnsonMG DeGroote Institute for Infectious Disease Research and the Department of Pathology and Molecular Medicine, McMaster University, Ontario, Canada.
Chris B Stone
David C Bulir
Brian K Coombes
James B Mahony
McMaster University · CASt. Joseph’s Healthcare Hamilton · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

backgroundWe have shown previously that Chlamydophila pneumoniae contains a dual-specific Ser/Thr protein kinase that phosphorylates CdsD, a structural component of the type III secretion apparatus. To further study the role of PknD in growth and development we sought to identify a PknD inhibitor to determine whether PknD activity is required for replication.

resultsUsing an in vitro kinase assay we screened 80 known eukaryotic protein kinase inhibitors for activity against PknD and identified a 3'-pyridyl oxindole compound that inhibited PknD autophosphorylation and phosphorylation of CdsD. The PknD inhibitor significantly retarded the growth rate of C. pneumoniae as evidenced by the presence of very small inclusions with a reduced number of bacteria as seen by electron microscopy. These inclusions contained the normal replicative forms including elementary bodies (EB), intermediate bodies (IB) and reticulate bodies (RB), but lacked persistent bodies (PB), indicating that induction of persistence was not the cause of reduced chlamydial growth. Blind passage of C. pneumoniae grown in the presence of this PknD inhibitor for 72 or 84 hr failed to produce inclusions, suggesting this compound blocks an essential step in the production of infectious chlamydial EB. The compound was not toxic to HeLa cells, did not block activation of the MEK/ERK pathway required for chlamydial invasion and did not block intracellular replication of either Chlamydia trachomatis serovar D or Salmonella enterica sv. Typhimurium suggesting that the inhibitory effect of the compound is specific for C. pneumoniae.

conclusionWe have identified a 3'-pyridyl oxindole compound that inhibits the in vitro kinase activity of C. pneumoniae PknD and inhibits the growth and production of infectious C. pneumoniae progeny in HeLa cells. Together, these results suggest that PknD may play a key role in the developmental cycle of C. pneumoniae.

Indexed as

Bacterial ProteinsCell SurvivalChlamydophila InfectionsChlamydophila pneumoniaeGene Expression Regulation, BacterialHeLa CellsHumansIndolesOxindolesPhosphorylationProtein Kinase CProtein Kinase Inhibitors2-oxindoleBacterial ProteinsIndolesOxindolesProtein Kinase Cprotein kinase DProtein Kinase Inhibitors

Identifiers

PMID19828035
PMCPMC2765968
OpenAlexW2159809801

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.