Gene Editing of a Carcinogenic Liver Fluke Tetraspanin Impairs Parasite Surface Biogenesis and Extracellular Vesicle Uptake by Human Host Cells
1
Issued Date
2026-02-18
Resource Type
eISSN
15376613
Scopus ID
2-s2.0-105030511007
Pubmed ID
40905941
Journal Title
Journal of Infectious Diseases
Volume
233
Issue
2
Start Page
e510
End Page
e520
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Infectious Diseases Vol.233 No.2 (2026) , e510-e520
Suggested Citation
Chaiyadet S., Ittiprasert W., Smout M.J., Khowawisetsut L., Ruangsuwast A., Brindley P.J., Loukas A., Laha T. Gene Editing of a Carcinogenic Liver Fluke Tetraspanin Impairs Parasite Surface Biogenesis and Extracellular Vesicle Uptake by Human Host Cells. Journal of Infectious Diseases Vol.233 No.2 (2026) , e510-e520. e520. doi:10.1093/infdis/jiaf466 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/115399
Title
Gene Editing of a Carcinogenic Liver Fluke Tetraspanin Impairs Parasite Surface Biogenesis and Extracellular Vesicle Uptake by Human Host Cells
Corresponding Author(s)
Other Contributor(s)
Abstract
Opisthorchiasis remains a significant public health concern throughout Southeast Asia. The liver fluke Opisthorchis viverrini resides within the biliary tract, and chronic infection leads to bile duct cancer, or cholangiocarcinoma. Here, we examined the functions of liver fluke tetraspanins, 4-transmembrane domain proteins expressed on the surface of the fluke tegument, and extracellular vesicles (EVs) derived from this syncytial surface. We undertook CRISPR-Cas9 gene knockout (KO) of the O viverrini tetraspanin 2 (Ov-tsp-2) gene and found that Ov-tsp-2-KO flukes had abnormal tegument biogenesis. The tegument of Ov-tsp-2-KO flukes was increasingly vacuolated, and fewer EVs were secreted. EVs that were secreted were deficient in Ov-TSP-2, and their uptake by cholangiocytes was diminished. The findings indicate a critical role for Ov-TSP-2 in maintenance of the tegument, EV production, and uptake by host target cells; they also support the development of this parasite antigen as an anti-infection and anticancer vaccine for opisthorchiasis and opisthorchiasis-associated cholangiocarcinoma.