Evidence map›Paper›PMID 41276610›Full record

ArticleCommunications biology2025

Dcaf15-mediated EphA2 degradation triggers disruption of the blood-brain barrier during Streptococcus suis meningitis.

Hang Yin, Shiqi Lang, Yi Lu, Zeyu Zhou, Shuying Ren, Xiaoying Yu, Jianqiao Qiu, Zhiwei Li, Xiangru Wang, Lianci Peng and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

11 authors.

Hang Yin *Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, Beibei, China.
Shiqi Lang *Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, Beibei, China.
Yi Lu *Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, Beibei, China.
Zeyu ZhouJoint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, Beibei, China.
Shuying RenJoint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, Beibei, China.
Xiaoying YuJoint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, Beibei, China.
Jianqiao QiuJoint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, Beibei, China.
Zhiwei LiJoint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, Beibei, China.
Xiangru WangNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China. wangxr228@mail.hzau.edu.cn.ORCID http://orcid.org/0000-0003-0191-1378
Lianci PengJoint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, Beibei, China. penglianci@swu.edu.cn.ORCID http://orcid.org/0000-0002-9005-3186
Rendong FangJoint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing, Beibei, China. rdfang@swu.edu.cn.ORCID http://orcid.org/0000-0003-3094-5059

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Disruption of blood-brain barrier (BBB) is the critical step of Streptococcus suis (S. suis) meningitis. Here we show that Ephrin type-A receptor 2 (EphA2) plays an important role in BBB against S. suis meningitis. S. suis downregulates EphA2 and EphA2 deficiency aggravates S. suis-induced BBB disruption in vitro and in vivo. We identify that EphA2-mediated autophagy alleviates S. suis-induced BBB disruption. To destroy the protective effect of EphA2 in BBB, S. suis recruits E3 ligase DCAF15 to interact with EphA2, which induces EphA2 ubiquitination and degradation. Mechanically, DCAF15 promotes K48- and K63-linked ubiquitination of EphA2 at K646, K649 and K754. In addition, S. suis serine/threonine protein kinase (STK) is indispensable for EphA2 degradation. STK phosphorylates histone deacetylase SIRT1 at S48 to trigger the deacetylation of DCAF15, enhancing DCAF15-EphA2 interaction and promoting ubiquitinated degradation of EphA2, thereby disrupting BBB. Moreover, acetylation of DCAF15 at K552 and K581 sites is involved in mediating EphA2 ubiquitination and BBB stability. Our study suggests a protective role of EphA2 in S. suis-induced BBB disruption, which provides a valuable insight on the development of EphA2 as a potential therapeutic target to treat bacterial meningitis.

Indexed as

Blood-Brain BarrierMeningitis, BacterialReceptor, EphA2Streptococcal InfectionsStreptococcus suisUbiquitin-Protein LigasesAcetylationAnimalsHumansMiceProteolysisUbiquitinationReceptor, EphA2Ubiquitin-Protein Ligases

Identifiers

PMID41276610
PMCPMC12749825

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.