Evidence map›Paper›PMID 41902461›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

A Bifunctional T3SS-Effector Simultaneously Cleaves Host MAP Kinase and Inhibits PPM1A Phosphatase.

Yaakov Socol, Lihi Gur-Arie, Netanel Tzarum, Tamara Wellins, Naama Katsowich, Miriam Ravins, Michal Bejerano-Sagie, Klil Cohen, Oded Livnah, Joshua N Adkins and 9 more

Abstract read
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In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Yaakov SocolDepartment of Microbiology and Molecular Genetics, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Lihi Gur-ArieDepartment of Microbiology and Molecular Genetics, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Netanel TzarumDepartment of Biological Chemistry, Alexander Silverman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Tamara WellinsDepartment of Biological Chemistry, Alexander Silverman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Naama KatsowichDepartment of Microbiology and Molecular Genetics, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Miriam RavinsDepartment of Microbiology and Molecular Genetics, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Michal Bejerano-SagieDepartment of Microbiology and Molecular Genetics, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Klil CohenDepartment of Microbiology and Molecular Genetics, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Oded LivnahThe Wolfson Center for Applied Structural Biology, The Edmond J. Safra Campus, The Hebrew University of Jerusalem, Jerusalem, Israel.
Joshua N AdkinsBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Ernesto NakayasuBiological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
Alexei SavchenkoDepartment of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
Yeu Khai ChoongDepartment of Biological Sciences, National University of Singapore, Singapore, Singapore.
Nikhil Kumar TulsianDepartment of Biological Sciences, National University of Singapore, Singapore, Singapore.
Saturo MachidaDepartment of Biological Sciences, National University of Singapore, Singapore, Singapore.
Sigal Ben-YehudaDepartment of Microbiology and Molecular Genetics, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Yael LitvakDepartment of Biological Chemistry, Alexander Silverman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
J SivaramanDepartment of Biological Sciences, National University of Singapore, Singapore, Singapore.
Ilan RosenshineDepartment of Microbiology and Molecular Genetics, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.ORCID https://orcid.org/0000-0001-7396-3586

Funding

European Research Council 810186Israel Science Foundation 1342/20Israel Science Foundation 3489/25Ministry of Education (MoE), Singapore A-8001519-00-00Ministry of Education (MoE), Singapore A-8002015-00-00Ministry of Education (MoE), Singapore A-8002957-00-00Ministry of Education (MoE), Singapore A-8004053-00-00
6 · The paper itself

Abstract

NleD belongs to a family of metalloproteases produced by multiple pathogens and functions as a Type III secretion system (T3SS) effector. NleD inactivates the p38 and JNK MAP kinases by cleaving them at a single site within the conserved threonine-X-tyrosine (TXY) motif. Here, we show that NleD from enteropathogenic E. coli (EPEC) interacts with PPM1A, a host metallophosphatase that targets multiple substrates, including the MAPK TXY motif. Binding of NleD inhibits the phosphatase activity of PPM1A while preserving NleD's proteolytic function. Structural analysis of the NleD-PPM1A complex reveals that NleD suppresses PPM1A activity by blocking phospho-protein substrates from accessing its catalytic pocket. Intriguingly, using a Citrobacter rodentium murine infection model, we found that NleD can enhance intestinal colonization in a manner independent of its protease activity, possibly via interaction with PPM1A. Together, these findings identify NleD as a bifunctional effector, highlighting the sophisticated strategies by which T3SS effectors manipulate key host signaling pathways.

Indexed as

Enteropathogenic Escherichia coliEscherichia coli ProteinsMitogen-Activated Protein KinasesProtein Phosphatase 2CAnimalsHumansMiceEscherichia coli ProteinsMitogen-Activated Protein KinasesPPM1A protein, humanProtein Phosphatase 2Centeropathogenic E. coliJNKMAPKNleDNleEp38PPM1A

Identifiers

PMID41902461
PMCPMC13325838

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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.