Deletion of the gsk-3β (Glycogen synthase kinase-3β) in zebrafish results in decreased susceptibility to Aeromonas hydrophila

Microb Pathog. 2024 Nov 16:198:107129. doi: 10.1016/j.micpath.2024.107129. Online ahead of print.

Abstract

Aeromonas hydrophila is a significant pathogen in the field of fish farming, resulting in substantial financial losses for the aquaculture industry. As the pathogen's resistance to commercially available antibiotics continues to rise, the identification of novel antimicrobial strategies becomes increasingly crucial. This study aims to explore the modulatory impact of gsk-3β (Glycogen synthase kinase-3β) on the intrinsic immunity against Aeromonas hydrophila in zebrafish, with the objective of uncovering a new avenue for enhancing fish antimicrobial activity through gene editing. Our investigation involved an analysis of the evolutionary patterns and protein sequence of gsk-3β, elucidating its conserved characteristics in zebrafish and fish species of economic importance. In this research, CRISPR-Cas9 technology was employed to generate a zebrafish model with a knockout of gsk-3β, resulting in a decreased resistance of zebrafish to Aeromonas hydrophila (ATCC 7966) infection. Furthermore, we conducted preliminary investigations into the potential mechanisms through which gsk-3β governs antimicrobial immunity. Our findings revealed that knockout of gsk-3β resulted in diminished activation of innate immunity, antioxidant capacity, and autophagy. Hence, the findings of this study are highly significant in improving the economic benefits of aquaculture and in effectively preventing and controlling infection caused by Aeromonas hydrophila.

Keywords: Aeromonas hydrophila; Gsk-3β (Glycogen synthase kinase-3β); Immune response; Knockout; Zebrafish.