Evidence map›Paper›PMID 40906790›Full record

ArticlePLoS neglected tropical diseases2025

Kinome analysis of Madurella mycetomatis identified kinases in the cell wall integrity pathway as novel potential therapeutic drug targets in eumycetoma caused by Madurella mycetomatis.

Mickey Konings, Nikolaos Strepis, Ri-Ichiroh Manabe, Akira Hasegawa, Somdatta Chaudhari, Saskia du Pré, Marij Schippers, Michihira Tagami, Jingyi Ma, Yasushi Okazaki and 7 more

Abstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

17 authors.

Mickey KoningsDepartment of Medical Microbiology and Infectious Diseases Rotterdam, Erasmus Medical Center, University Medical Centre, Rotterdam, The Netherlands.
Nikolaos StrepisDepartment of Medical Microbiology and Infectious Diseases Rotterdam, Erasmus Medical Center, University Medical Centre, Rotterdam, The Netherlands.
Ri-Ichiroh ManabeLaboratory for Comprehensive Genomic Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
Akira HasegawaLaboratory for Large-Scale Biomedical Data Technology, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
Somdatta ChaudhariDepartment of Pharmaceutical Chemistry, Progressive Education society's Modern College of Pharmacy, Pune, Maharashtra, India.
Saskia du PréDepartment of Medical Microbiology and Infectious Diseases Rotterdam, Erasmus Medical Center, University Medical Centre, Rotterdam, The Netherlands.
Marij SchippersDepartment of Medical Microbiology and Infectious Diseases Rotterdam, Erasmus Medical Center, University Medical Centre, Rotterdam, The Netherlands.
Michihira TagamiLaboratory for Comprehensive Genomic Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
Jingyi MaDepartment of Medical Microbiology and Infectious Diseases Rotterdam, Erasmus Medical Center, University Medical Centre, Rotterdam, The Netherlands.
Yasushi OkazakiLaboratory for Comprehensive Genomic Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
Matthew ToddSchool of Pharmacy and Structural Genomics Consortium, University College London, London, United Kingdom.
Bernhard BiersackOrganic Chemistry Laboratory, University Bayreuth, Bayreuth, Germany.
Vijay MasandDepartment of Chemistry, Vidya Bharati Mahavidyalaya, Amravati, Maharashtra, India.
Annelies VerbonDepartment of Medical Microbiology and Infectious Diseases Rotterdam, Erasmus Medical Center, University Medical Centre, Rotterdam, The Netherlands.
Takeya KasukawaLaboratory for Large-Scale Biomedical Data Technology, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
Imad AbugessaisaLaboratory for Large-Scale Biomedical Data Technology, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
Wendy W J van de SandeDepartment of Medical Microbiology and Infectious Diseases Rotterdam, Erasmus Medical Center, University Medical Centre, Rotterdam, The Netherlands.ORCID 0000-0002-8652-8783

Funding

Erasmus University, Rotterdam, The NetherlandsEUR FellowshipJapanese Ministry of Education, Culture, Sports, Science and Technology MEXTThe Japan Society for the Promotion of Science, KAKENHI
6 · The paper itself

Abstract

Eumycetoma is a neglected tropical subcutaneous disease most commonly caused by the fungus Madurella mycetomatis. Currently, eumycetoma is treated by a combination of antifungal therapy and surgery, with limited success rates. To identify novel drug targets we used an in silico approach to determine the kinases present in M. mycetomatis genome and rank them as potential drug targets. In total 132 predicted kinases were identified in M. mycetomatis, of which 21 were predicted to be essential for fungal viability and 4 of these had no human orthologues. Two were linked to the Cell Wall Integrity (CWI) signalling pathway and were expressed in a Galleria mellonella infection model. Several kinase inhibitors were identified after in silico modelling, however only 8 were able to inhibit growth. Five had predicted binding affinity with components of the CWI. Altogether, the CWI shows potential as a drug target for further evaluation.

Indexed as

Antifungal AgentsCell WallFungal ProteinsMadurellaMycetomaPhosphotransferasesAnimalsHumansMothsProtein Kinase InhibitorsSignal TransductionAntifungal AgentsFungal ProteinsPhosphotransferasesProtein Kinase Inhibitors

Identifiers

PMID40906790
PMCPMC12425257

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Registered trials

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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.