Evidence map›Paper›PMID 24848868›Full record

ArticleEndocrinology2014

Pseudomonas aeruginosa elastase disrupts the cortisol-binding activity of corticosteroid-binding globulin.

Marc Simard, Lesley A Hill, Caroline M Underhill, Bernd O Keller, Ivan Villanueva, Robert E W Hancock, Geoffrey L Hammond

Open access · bronzeAbstract read
In one paragraph

Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.9field-weighted citation impact, top 16% 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

21 citing papers in PubMed, 35 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Early life stress causes persistent impacts on the microbiome of Atlantic salmon.Comparative biochemistry and physiology. Part D, Genomics & proteomics · 2021
    Article
  7. Article
  8. Article
  9. Article
  10. Functional implications of corticosteroid-binding globulinJournal of molecular endocrinology · 2018
    Article
  11. Article
  12. Review
  13. CRH Affects the Phenotypic Expression of Sepsis-Associated Virulence Factors byFrontiers in cellular and infection microbiology · 2017
    Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Structural characterization of zinc-bound Zmp1, a zinc-dependent metalloprotease secreted by Clostridium difficile.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2016
    Article
  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

7 authors at 2 institutions in 1 country.

Marc SimardDepartment of Cellular and Physiological Sciences (M.S., L.A.H., C.M.U., G.L.H.), University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada, V6T 1Z3; Department of Pathology and Laboratory Medicine (B.O.K.), University of British Columbia, Child and Family Research Institute, 950 W 28th Ave, Vancouver, British Columbia, Canada, V5Z 4H4; Department of Microbiology and Immunology (I.V.), University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada, V6T 1Z3; and Department of Microbiology and Immunology (R.E.W.H.), University of British Columbia, Centre for Microbial Diseases and Immunity Research, 2259 Lower Mall Research Station, Vancouver, British Columbia, Canada, V6T 1Z4.
Lesley A Hill
Caroline M Underhill
Bernd O Keller
Ivan Villanueva
Robert E W Hancock
Geoffrey L Hammond
University of British Columbia · CAChild and Family Research Institute · CA

Funding

Translational Research Center to Expedite Novel Therapies in Cystic FibrosisP30DK089507 · NIDDK · SEATTLE CHILDREN'S HOSPITAL · PI Christopher Hooper Goss, Lucas R Hoffman · 2010 to 2026
$21.4M
CIHR MOP-111102NIDDK NIH HHS P30 DK089507NIDDK NIH HHS P30DK089507
6 · The paper itself

Abstract

The serine protease inhibitor (SERPIN) family member corticosteroid-binding globulin (CBG) is the main carrier of glucocorticoids in plasma. Human CBG mediates the targeted release of cortisol at sites of inflammation through cleavage of its reactive center loop (RCL) by neutrophil elastase. The RCLs of SERPIN family members are targeted by diverse endogenous and exogenous proteases, including several bacterial proteases. We tested different bacteria for their ability to secrete proteases that disrupt CBG cortisol-binding activity, and characterized the responsible protease and site of CBG cleavage. Serum CBG integrity was assessed by Western blotting and cortisol-binding capacity assay. Effects of time, pH, temperature, and protease inhibitors were tested. Proteolytically active proteins from bacterial media were purified by fast protein liquid chromatography, and the active protease and CBG cleavage sites were identified by mass spectrometry. Among the bacteria tested, medium from Pseudomonas aeruginosa actively disrupted the cortisol-binding activity of CBG. This proteolytic activity was inhibited by zinc chelators and occurred most efficiently at pH 7 and elevated physiological temperature (ie, 41°C). Mass spectrometric analysis of a semi-purified fraction of P. aeruginosa media identified the virulence factor LasB as the responsible protease, and this was confirmed by assaying media from LasB-deficient P. aeruginosa. This metalloprotease cleaves the CBG RCL at a major site, distinct from that targeted by neutrophil elastase. Our results suggest that humoral responses to P. aeruginosa infection are influenced by this pathogen's ability to secrete a protease that promotes the release of the anti-inflammatory steroid, cortisol, from its plasma transport protein.

Indexed as

Bacterial ProteinsCulture Media, ConditionedHumansHydrocortisoneHydrogen-Ion ConcentrationLeukocyte ElastaseMetalloendopeptidasesPseudomonas aeruginosaTemperatureTosyllysine Chloromethyl KetoneTranscortinVirulence FactorsZincBacterial ProteinsCulture Media, ConditionedHydrocortisoneLeukocyte ElastaseMetalloendopeptidasespseudolysin, Pseudomonas aeruginosaTosyllysine Chloromethyl KetoneTranscortinVirulence FactorsZinc

Identifiers

PMID24848868
PMCPMC4098004
OpenAlexW2006901432

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.