时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
However, the metabolic regulatory mechanisms that control SNARE protein stability and turnover remain incompletely characterized.；Despite their critical roles, the molecular mechanisms by which these effectors interface with host proteostatic metabolism to control SNARE-dependent membrane fusion remain largely elusive.；Given that the UPS controls the turnover of most cellular proteins (), we hypothesized that C. burnetii may target UPS-mediated SNARE proteostasis to tune lysosomal metabolic maturation.
方法
All procedures for animal experiments were approved by the Institute of Animal Care and Use Committee (IACUC) of the Academy of Military Medical Sciences (approval no.；Severe combined immune deficiency (SCID) mice (aged 6 to 8 weeks) were purchased from the Vital River Laboratory (Beijing, China).；The expression of CelF in the NMIIpTEM1-CelF and dotA::Tn pTEM1-CelF strains was verified by Western blotting using an anti-FLAG antibody.；For the NMIIpdCas9 and NMIIpdCas9-sgCelF (designated CelF KD) strains, the expression levels of celF and dCas9 were determined by reverse transcription quantitative PCR (RT-qPCR) using primers specific for the deleted or introduced genes, with primers targeting rpoB as a control.
核心结论
The CelF KD strain grew normally in ACCM-2 medium () but was significantly impaired in THP-1 cells ().；To assess the role of CelF in the virulence of C. burnetii, SCID mice () were infected with the NMII, NMIIpdCas9, or CelF KD strains.；Infection with the NMII strain resulted in significant splenomegaly compared with uninfected controls (). ‖ 结论：These findings advance our understanding of host-pathogen metabolic interactions and provide fundamental insights into the proteostatic control of membrane fusion machinery.
局限
Our study has several limitations that warrant further investigation.；Future in vivo validation with a complemented strain is warranted.
对本项目的价值
★☆☆☆☆ 营养感知与自噬轴决定「干预窗口 + 剂量方案」，是组合疗法的时间锚。
全文来源
PMC JATS 全文（正文 39,880 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Coxiella burnetii effector CelF reprograms host proteostasis via competitive disruption of the UBQLN1-PSMD4 axis to stabilize autophagic SNARE SNAP29 and modulate lysosomal metabolic maturation.
- 期刊与标识：Front Physiol · PMID 42952505 · DOI 10.3389/fphys.2026.1957980
B 级证据分级：B 级（同行评议临床前研究，主要为动物模型）
本文核心结论来自动物模型或体外细胞学，属临床前证据，不能外推至人体。「延长健康寿命」「改善功能」等表述在小鼠中的意义，与人类临床结局之间仍有距离。
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