Evidence map›Paper›PMID 29683762›Full record

ArticleVirulence2018

Regulation of hemolysin in uropathogenic Escherichia coli fine-tunes killing of human macrophages.

Ambika M V Murthy, Minh-Duy Phan, Kate M Peters, Nguyen Thi Khanh Nhu, Rodney A Welch, Glen C Ulett, Mark A Schembri, Matthew J Sweet

Open access · goldAbstract read
In one paragraph

Article in Virulence, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

19 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Article
  3. Current research in microbial sciences · 2025
    Article
  4. Article
  5. Article
  6. Nucleotide receptors mediate protection against neonatal sepsis and meningitis caused by alpha-hemolysin expressing Escherichia coli K1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  7. Microorganisms · 2022
    Review
  8. Article
  9. "Omics" Technologies - What Have They Told Us About UropathogenicFrontiers in cellular and infection microbiology · 2022
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. UropathogenicProceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  18. Comparative Genome Analysis of UropathogenicFrontiers in cellular and infection microbiology · 2019
    Article
  19. Heme Uptake and Utilization by Gram-Negative Bacterial Pathogens.Frontiers in cellular and infection microbiology · 2019
    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

8 authors at 3 institutions in 2 countries.

Ambika M V Murthya Institute for Molecular Bioscience (IMB), IMB Centre for Inflammation and Disease Research, and the Australian Infectious Diseases Research Centre, The University of Queensland , QLD , Australia.ORCID 0000-0002-9767-1999
Minh-Duy Phanb School of Chemistry and Molecular Biosciences, and the Australian Infectious Diseases Research Centre, The University of Queensland , QLD , Australia.ORCID 0000-0002-3426-1044
Kate M Petersb School of Chemistry and Molecular Biosciences, and the Australian Infectious Diseases Research Centre, The University of Queensland , QLD , Australia.
Nguyen Thi Khanh Nhub School of Chemistry and Molecular Biosciences, and the Australian Infectious Diseases Research Centre, The University of Queensland , QLD , Australia.
Rodney A Welchc Department of Medical Microbiology and Immunology , University of Wisconsin School of Medicine and Public Health , Madison , WI , USA.
Glen C Ulettd School of Medical Science, and Menzies Health Institute Queensland, Griffith University , QLD , Australia.
Mark A Schembrib School of Chemistry and Molecular Biosciences, and the Australian Infectious Diseases Research Centre, The University of Queensland , QLD , Australia.ORCID 0000-0003-4863-9260
Matthew J Sweeta Institute for Molecular Bioscience (IMB), IMB Centre for Inflammation and Disease Research, and the Australian Infectious Diseases Research Centre, The University of Queensland , QLD , Australia.ORCID 0000-0002-0406-8139
The University of Queensland · AUGriffith University · AUUniversity of Wisconsin–Madison · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Uropathogenic E. coli (UPEC) causes the majority of urinary tract infections (UTIs), which are a major global public health concern. UPEC uses numerous mechanisms to subvert the innate immune system, including targeting macrophage functions. We recently showed that some UPEC strains rapidly kill human macrophages via an NLRP3-independent pathway, and also trigger NLRP3-dependent IL-1β processing. In this study, we used random transposon mutagenesis in the reference strain CFT073 to identify UPEC genes that mediate human macrophage cell death. Our approach revealed that the hemolysin A (HlyA) toxin is essential for triggering both cell death and NLRP3 inflammasome-mediated IL-1β release in human macrophages. Random transposon mutagenesis also identified the cof gene, which encodes a poorly characterized phosphatase, as a novel hemolysin regulator; a CFT073 mutant deleted for the cof gene secreted significantly reduced levels of HlyA, had diminished hemolytic activity, and was impaired in its capacity to trigger human macrophage cell death and IL-1β release. Together, our findings reveal that Cof fine-tunes production of hemolysin, an important determinant of both UPEC-mediated inflammasome activation and human macrophage cell death.

Indexed as

Gene Expression Regulation, BacterialAnimalsApoptosisCell LineEscherichia coli InfectionsEscherichia coli ProteinsHemolysin ProteinsHumansInflammasomesInterleukin-1betaMacrophagesPhosphoric Monoester HydrolasesUrinary Tract InfectionsUropathogenic Escherichia coliEscherichia coli ProteinsHemolysin ProteinsHlya protein, E coliInflammasomesInterleukin-1betaPhosphoric Monoester Hydrolasescell deathcofgene regulationinflammasomemacrophageUPECurinary tract infectionα-hemolysin

Identifiers

PMID29683762
PMCPMC5989160
OpenAlexW2801296074

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.