Evidence map›Paper›PMID 20605985›Full record

ArticleInfection and immunity2010

Activation of the CpxRA system by deletion of cpxA impairs the ability of Haemophilus ducreyi to infect humans.

Stanley M Spinola, Kate R Fortney, Beth Baker, Diane M Janowicz, Beth Zwickl, Barry P Katz, Robert J Blick, Robert S Munson

Open access · greenAbstract read
In one paragraph

Article in Infection and immunity, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.1field-weighted citation impact, top 10% 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

44 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Anti-infective compounds forSustainable microbiology · 2026
    Review
  5. Molecular pathogenesis ofMicrobiology and molecular biology reviews : MMBR · 2025
    Review
  6. Review
  7. Cpx-signalling innpj antimicrobials and resistance · 2024
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Interactions of the Skin PathogenFrontiers in immunology · 2020
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. The Virulence Effect of CpxRA inFrontiers in cellular and infection microbiology · 2018
    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

8 authors at 3 institutions in 2 countries.

Stanley M SpinolaDepartment of Medicine, Indiana University, 224 Medical Science Building, 635 Barnhill Drive, Indianapolis, IN 46202-5124, USA. sspinola@iupui.edu
Kate R Fortney
Beth Baker
Diane M Janowicz
Beth Zwickl
Barry P Katz
Robert J Blick
Robert S Munson
Bipar · FRPediatrics and Genetics · USThe University of Texas Southwestern Medical Center · US

Funding

VIRAL DETERMINANTS OF HSV DISEASE IN MICEU19AI031494 · NIAID · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SPINOLA, STANLEY M. · 1995 to 2009
$13.6M
PATHOGENESIS OF HAEMOPHILUS DUCREYI INFECTIONSR01AI027863 · NIAID · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SPINOLA, STANLEY M. · 1995 to 2013
$3.8M
PATHOGENESIS OF HAEMOPHILUS DUCREYI INFECTIONSR29AI027863 · NIAID · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI SPINOLA, STANLEY M · 1990 to 1994
–
VARIABILITY IN HERPES SIMPLEX VIRUS GLYCOPROTEINS AND INFECTIVITYU01AI031494 · NIAID · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI BYRNE, GERALD I · 1991 to 1994
–
NCRR NIH HHS UL RR052761NIAID NIH HHS AI27863NIAID NIH HHS AI31494NIAID NIH HHS R01 AI027863NIAID NIH HHS U19 AI031494NIAID NIH HHS U19 AI31494
6 · The paper itself

Abstract

Haemophilus ducreyi must adapt to the environment of the human host to establish and maintain infection in the skin. Bacteria generally utilize stress response systems, such as the CpxRA two-component system, to adapt to hostile environments. CpxRA is the only obvious two-component system contained in the H. ducreyi genome and negatively regulates the lspB-lspA2 operon, which encodes proteins that enable the organism to resist phagocytosis. We constructed an unmarked, in-frame H. ducreyi cpxA deletion mutant, 35000HPDeltacpxA. In human inoculation experiments, 35000HPDeltacpxA formed papules at a rate and size that were significantly less than its parent and was unable to form pustules compared to the parent. CpxA usually has kinase and phosphatase activities for CpxR, and the deletion of CpxA leads to the accumulation of activated CpxR due to the loss of phosphatase activity and the ability of CpxR to accept phosphate groups from other donors. Using a reporter construct, the lspB-lspA2 promoter was downregulated in 35000HPDeltacpxA, confirming that CpxR was activated. Deletion of cpxA downregulated DsrA, the major determinant of serum resistance in the organism, causing the mutant to become serum susceptible. Complementation in trans restored parental phenotypes. 35000HPDeltacpxA is the first H. ducreyi mutant that is impaired in its ability to form both papules and pustules in humans. Since a major function of CpxRA is to control the flow of protein traffic across the periplasm, uncontrolled activation of this system likely causes dysregulated expression of multiple virulence determinants and cripples the ability of the organism to adapt to the host.

Indexed as

AdultBacterial Outer Membrane ProteinsBacterial ProteinsFemaleGene DeletionHaemophilus ducreyiHumansLectinsMaleMiddle AgedProtein KinasesBacterial Outer Membrane ProteinsBacterial ProteinsCpxA protein, bacteriaCpxR protein, BacteriaLectinsLspA2 protein, Haemophilus ducreyiLspB protein, Haemophilus ducreyiProtein Kinases

Identifiers

PMID20605985
PMCPMC2937468
OpenAlexW2159612861

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.