Evidence map›Paper›PMID 37399210›Full record

ArticlePLoS pathogens2023

Macrophage infectivity potentiator protein, a peptidyl prolyl cis-trans isomerase, essential for Coxiella burnetii growth and pathogenesis.

Aleksandra W Debowski, Nicole M Bzdyl, David R Thomas, Nichollas E Scott, Christopher H Jenkins, Jua Iwasaki, Emily A Kibble, Chen Ai Khoo, Nicolas J Scheuplein, Pamela M Seibel and 9 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.2field-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

6 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
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  5. Article
  6. Inhibition of macrophage infectivity potentiator inFrontiers in cellular and infection microbiology · 2024
    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

19 authors at 7 institutions in 3 countries.

Aleksandra W DebowskiMarshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia.
Nicole M BzdylMarshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia.
David R ThomasDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
Nichollas E ScottDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
Christopher H JenkinsDefence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom.
Jua IwasakiMarshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia.
Emily A KibbleMarshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia.
Chen Ai KhooDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
Nicolas J ScheupleinInstitute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, Würzburg, Germany.
Pamela M SeibelSchool of Molecular Sciences, The University of Western Australia, Crawley, Western Australia, Australia.
Theresa LohrInstitute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, Würzburg, Germany.
Georgie MettersDefence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom.
Charles S BondSchool of Molecular Sciences, The University of Western Australia, Crawley, Western Australia, Australia.
Isobel H NorvilleDefence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom.
Keith A StubbsSchool of Molecular Sciences, The University of Western Australia, Crawley, Western Australia, Australia.
Nicholas J HarmerDepartment of Biosciences, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter, United Kingdom.
Ulrike HolzgrabeInstitute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, Würzburg, Germany.
Hayley J NewtonDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
Mitali Sarkar-TysonMarshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia.ORCID 0000-0002-6764-8499
The University of Western Australia · AUThe University of Melbourne · AUDefence Science and Technology Laboratory · GBUniversity of Würzburg · DEMurdoch University · AUThe Kids Research Institute Australia · AUUniversity of Exeter · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Coxiella burnetii is a Gram-negative intracellular pathogen that causes the debilitating disease Q fever, which affects both animals and humans. The only available human vaccine, Q-Vax, is effective but has a high risk of severe adverse reactions, limiting its use as a countermeasure to contain outbreaks. Therefore, it is essential to identify new drug targets to treat this infection. Macrophage infectivity potentiator (Mip) proteins catalyse the folding of proline-containing proteins through their peptidyl prolyl cis-trans isomerase (PPIase) activity and have been shown to play an important role in the virulence of several pathogenic bacteria. To date the role of the Mip protein in C. burnetii pathogenesis has not been investigated. This study demonstrates that CbMip is likely to be an essential protein in C. burnetii. The pipecolic acid derived compounds, SF235 and AN296, which have shown utility in targeting other Mip proteins from pathogenic bacteria, demonstrate inhibitory activities against CbMip. These compounds were found to significantly inhibit intracellular replication of C. burnetii in both HeLa and THP-1 cells. Furthermore, SF235 and AN296 were also found to exhibit antibiotic properties against both the virulent (Phase I) and avirulent (Phase II) forms of C. burnetii Nine Mile Strain in axenic culture. Comparative proteomics, in the presence of AN296, revealed alterations in stress responses with H2O2 sensitivity assays validating that Mip inhibition increases the sensitivity of C. burnetii to oxidative stress. In addition, SF235 and AN296 were effective in vivo and significantly improved the survival of Galleria mellonella infected with C. burnetii. These results suggest that unlike in other bacteria, Mip in C. burnetii is required for replication and that the development of more potent inhibitors against CbMip is warranted and offer potential as novel therapeutics against this pathogen.

Indexed as

Coxiella burnetiiQ FeverAnimalsBacteriaBacterial ProteinsHumansHydrogen PeroxideMacrophagesPeptidylprolyl IsomeraseBacterial ProteinsHydrogen PeroxidePeptidylprolyl Isomerase

Identifiers

PMID37399210
PMCPMC10348545
OpenAlexW4382931471

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.