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  3. Bergeyella cardium variant induces a unique cytoplasmic vacuolization cell death floatptosis in macrophage

Bergeyella cardium variant induces a unique cytoplasmic vacuolization cell death floatptosis in macrophage

  • Cell Discov. 2025 Oct 21;11(1):83. doi: 10.1038/s41421-025-00840-x.
Rudi Mao # 1 2,  Hongwei Pan # 3 4,  Luyu Yang # 1,  Zhenyu Fan # 1,  Yanfeng Li # 1,  Xinran Yu 1,  Zhen Li 1,  Ying Chen 3 4,  Yang Yu 5,  Wei Wang 5,  Chengjiang Gao 6,  Jun Peng 7,  Tao Xu 8,  Yi Zhang 9 10,  Xiaopeng Qi 11 12
Affiliations

Affiliations

  • 1 Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Clinical Laboratory/Qilu Hospital, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 2 Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jing-Wu Road, Jinan, China.
  • 3 Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, China.
  • 4 Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan, China.
  • 5 Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 6 Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province & Key Laboratory for Experimental Teratology of Ministry of Education, Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, China.
  • 7 Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 8 Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Clinical Laboratory/Qilu Hospital, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China. tao.xu@sdu.edu.cn.
  • 9 Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, China. yizhang@sdu.edu.cn.
  • 10 Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan, China. yizhang@sdu.edu.cn.
  • 11 Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Clinical Laboratory/Qilu Hospital, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China. xqi@email.sdu.edu.cn.
  • 12 State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. xqi@email.sdu.edu.cn.
  • # Contributed equally.
PMID: 41115953 DOI: 10.1038/s41421-025-00840-x
Abstract

Bacterial pathogens have evolved multiple mechanisms to modulate host cell death, evade host immunity, and establish persistent Infection. Here, we show that an infective endocarditis causative pathogen, Bergeyella cardium, is frequently detected in oral specimens from clinical patients. A variant strain of Bergeyella cardium (BCV) induces unique cytoplasmic vacuolization cell death and minor apoptosis-like cell death in macrophages. The cytoplasmic vacuolization cell death triggered by BCV is characterized by Fused LysosOme-Associated Termination (floatptosis) and is inhibited by the Sodium Channel Inhibitor amiloride. Moreover, outer membrane vesicles (OMVs) or transfection of barrel-like membrane proteins, lipocalin, β-barrel, and PorV, dramatically induce cytoplasmic vacuolization. Endosomal solute carrier family 9 member A9 (SLC9A9) plays important roles in the process of BCV-, OMVs-, and barrel-like proteins-triggered cytoplasmic vacuolization cell death via promoting vacuole fusion. SLC9A9 deficiency or amiloride administration increases host defense against BCV Infection. These findings contribute to developing novel approaches to modulate cytoplasmic vacuolization cell death and treat infectious diseases.

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