2. Academic Validation
  3. Salmonella Typhimurium persistently infects host via its effector SseJ-induced PHB2-mediated mitophagy

Salmonella Typhimurium persistently infects host via its effector SseJ-induced PHB2-mediated mitophagy

  • Autophagy. 2025 Feb 14:1-17. doi: 10.1080/15548627.2025.2462511.
Dage Sun 1,  Hongchao Gou 2,  Yu Zhang 3,  Jiayi Li 1,  Changzhi Dai 1,  Haiyan Shen 2,  Kaifeng Chen 1,  Yu Wang 1,  Peng Pan 1,  Ting Zhu 1,  Chenggang Xu 1,  Tongling Shan 4,  Ming Liao 1 5,  Jianmin Zhang 1
Affiliations

Affiliations

  • 1 National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Key Laboratory of Zoonoses, Ministry of Agriculture, Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Key Laboratory of Animal Vaccine Development, Ministry of Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  • 2 Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangdong Provincial Key Laboratory of Livestock Disease Prevention, Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province, Guangzhou, China.
  • 3 Department of Preventive Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai, China.
  • 4 Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
  • 5 Department of Preventive Veterinary Medicine, College of Animal Science and Technology, Zhongkai University of Agricultural Engineering, Guangzhou, China.
PMID: 39902787 DOI: 10.1080/15548627.2025.2462511
Abstract

Despite decades of research on effective methods to resist Salmonella enterica serovar Typhimurium (S. Typhimurium) pathogenicity, the mechanisms of S. Typhimurium-host interactions have not been fully determined. S. Typhimurium is characterized as an important zoonosis in public health worldwide because of its endemicity, high morbidity, and difficulty in applying control and prevention measures. Herein, we introduce a novel Bacterial factor, secretion system effector J (SseJ), and its interactive host protein, PHB2 (prohibitin 2). We explored whether SseJ affected S. Typhimurium replication and survival in the host. S. Typhimurium Infection caused severe mitochondrial damage and Mitophagy, which facilitated S. Typhimurium proliferation in cells. S. Typhimurium SseJ activated the PINK1 (PTEN induced kinase 1)-PRKN (parkin RBR E3 ubiquitin protein Ligase)-autophagosome-dependent Mitophagy pathway, aided by the Mitophagy receptor PHB2, for Bacterial survival and persistent Infection. Moreover, suppression of Mitophagy alleviated the pathogenicity of S. Typhimurium. In conclusion, S. Typhimurium Infection could be antagonized by targeting the SseJ-PHB2-mediated host mitochondrial Autophagy pathway.Abbreviation: ACTB: actin beta; BafA1: bafilomycin A1; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; co-IP: co-immunoprecipitation; CFU: colony-forming units; COX4/COXIV: cytochrome c oxidase subunit 4; CQ: chloroquine; hpi: h post-bacterial infection; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; Mdivi-1:mitophagy inhibitor mitochondrial division inhibitor 1; MFN2: mitofusin 2; MG132: z-leu-leu-leucinal; MOI: multiplicity of infection; mtDNA: mitochondrial DNA; PBS: phosphate-buffered saline; PGAM5: PGAM family member 5, mitochondrial serine/threonine protein phosphatase; PHB2: prohibitin 2; PINK1: PTEN induced kinase 1; qPCR: quantitative real-time reverse transcription PCR; Roc-A: Rocaglamide A; PRKN/Parkin: parkin RBR E3 ubiquitin protein ligase; SCVs: Salmonella-containing vacuoles; siRNA: small interfering RNA; SPI-2: Salmonella pathogenicity island 2; SseJ: secretion system effector J; S. Typhimurium: Salmonella enterica serovar Typhimurium; S.T-ΔSseJ: SseJ gene-deleted Salmonella Typhimurium strains; S.T-CΔSseJ: SseJ-complemented Salmonella Typhimurium strains; WT: wild-type.

Keywords

Mitophagy; PHB2; PINK1; PRKN; Salmonella Typhimurium; SseJ.

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