Role of UBC9 in the inflammatory response and pathogen susceptibility in zebrafish

Abstract

UBC9 is a key enzyme involved in SUMOylation, a post-translational modification that targets protein function, stability, transcriptional regulation, and localization to affect biological processes in host cells. Pathogens often target UBC9 by exploiting the host's SUMO system to modify their proteins with altered functionality, which in turn favors the pathogens' survival or invasion. Herein, we investigated the critical role of UBC9 in regulating the inflammatory response and susceptibility to Mycobacterium marinum (Mm) infection in zebrafish. We effectively knocked down the UBC9 expression using morpholino antisense oligonucleotides, which showed significant developmental abnormalities in zebrafish, particularly in cartilage formation. Our results indicated that UBC9 is essential for immune cell migration, as its knockdown led to impaired macrophage and neutrophil responses during inflammation. Furthermore, we investigated the impact of UBC9 on the zebrafish response to Mm, a close relative of the tuberculosis-causing bacterium. Our results showed that UBC9-knocked-down zebrafish displayed a slight increase in bacterial proliferation, suggesting a potential role of UBC9 in host's ability to control pathogen replication and spread. The study explores the complex interplay between UBC9 and the immune system and provides insights into the important role of UBC9 in immune regulation and pathogen defence.