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

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.