EccC3 is essential for pathogenesis of rough Mycobacterium abscessus in zebrafish

Abstract

Mycobacterium abscessus ( Mab ) is currently recognized as an extremely difficult-to-manage pathogen in patients with cystic fibrosis. The rough (R) morphotype of Mab is associated with chronic and more aggressive infections in patients than the smooth (S) morphotype. However, the mechanisms of pathogenesis of Mab R remain largely unexplored. In this study, we investigated the infection capacity and virulence of a Mab R mutant lacking a functional ESX-3 secretion system using the zebrafish model. The mutant was severely impaired in its ability to replicate in the larvae, and this was correlated with a significant increase in larvae survival, highlighting the critical role of ESX-3 in Mab R virulence. Overall, this emphasizes ESX-3 as an attractive drug target for future drug developments against Mab R lung diseases.