PUBLICATION
Neu1-Deficient Zebrafish Cells Exhibit Reduced Edwardsiella piscicida Infection Due to Altered Lysosomal Exocytosis and Membrane Dynamics
- Authors
- Ishi, M., Tsurusaki, A., Komatsu, M., Shiozaki, K.
- ID
- ZDB-PUB-250313-27
- Date
- 2025
- Source
- Fish & shellfish immunology : 110273110273 (Journal)
- Registered Authors
- Shiozaki, Kazuhiro
- Keywords
- none
- MeSH Terms
-
- Animals
- Cells, Cultured
- Edwardsiella*/physiology
- Enterobacteriaceae Infections*/genetics
- Enterobacteriaceae Infections*/immunology
- Enterobacteriaceae Infections*/microbiology
- Enterobacteriaceae Infections*/veterinary
- Exocytosis*
- Fish Diseases*/immunology
- Fish Diseases*/microbiology
- Lysosomes*/physiology
- Neuraminidase*/genetics
- Zebrafish*/genetics
- Zebrafish*/immunology
- Zebrafish Proteins*/genetics
- PubMed
- 40074189 Full text @ Fish Shellfish Immunol.
Citation
Ishi, M., Tsurusaki, A., Komatsu, M., Shiozaki, K. (2025) Neu1-Deficient Zebrafish Cells Exhibit Reduced Edwardsiella piscicida Infection Due to Altered Lysosomal Exocytosis and Membrane Dynamics. Fish & shellfish immunology. :110273110273.
Abstract
Edwardsiella piscicida is a Gram-negative intracellular pathogen causing Edwardsiellosis, leading to economic losses in aquaculture. While phagocytosis is its primary infection route, alternative entry pathways remain largely unexplored. Neu1 sialidase, a lysosomal enzyme in glycoconjugate degradation, was investigated for its role in E. piscicida infection using primary cultured cells derived from Neu1-KO zebrafish fin (Neu1-KO cells). Compared to wild-type (WT) cells, Neu1-KO cells exhibited lower infection rates, which were associated with enhanced lysosomal exocytosis. Infection was restored by the intracellular calcium chelator BAPTA-AM, highlighting the role of exocytosis. Leupeptin, a cysteine/serine protease inhibitor, increased E. piscicida infection in Neu1-KO cells. Neu1-KO cells exhibited lower rab10 expression and reduced membrane ruffling, which was restored by BAPTA-AM and leupeptin. Given the role of epidermal growth factor receptor (EGFR) signaling, we assessed its phosphorylation, which was reduced in Neu1-KO cells but restored by treatment with BAPTA-AM and leupeptin. This suggests that inhibiting lysosome exocytosis or extracellular protease activity may suppress EGFR phosphorylation. These findings indicate that the decreased E. piscicida infection in Neu1-KO cells resulted from enhanced lysosomal exocytosis, leading to increased extracellular protease secretion, subsequent EGFR inactivation by extracellular protease, and reduced EGFR-regulated ruffling. This study provides novel insights into the regulatory mechanisms of bacterial infection and lysosomal exocytosis, informing potential therapeutic strategies against intracellular pathogens.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping