The Mycobacterium fortuitum complex comprises several closely related species, causing pulmonary and extra-pulmonary infections. However, there is very limited knowledge about the disease pathogenesis involved in M. fortuitum infections, particularly due to the lack of suitable animal models. Using the zebrafish model, we show that embryos are susceptible to M. fortuitum infection in a dose-dependent manner. Furthermore, zebrafish embryos form granulomas from as early as 2 days post-infection, recapitulating critical aspects of mycobacterial pathogenesis observed in other pathogenic species. The formation of extracellular cords in infected embryos highlights a previously unknown pathogenic feature of M. fortuitum. The formation of large corded structures occurs also during in vitro growth, suggesting that this is not a host-adapted stress mechanism deployed during infection. Moreover, transient macrophage depletion led to rapid embryo death with increased extracellular cords, indicating that macrophages are essential determinants of M. fortuitum infection control. Importantly, morpholino depletion of the cystic fibrosis transmembrane conductance regulator (cftr) significantly increased embryo death, bacterial burden, bacterial cords and abscesses. There was a noticeable decrease in the number of cftr-deficient infected embryos with granulomas as compared to infected controls, suggesting that loss of CFTR leads to impaired host immune responses and confers hypersusceptiblity to M. fortuitum infection. Overall, these findings highlight the application of the zebrafish embryo to study M. fortuitum and emphasizes previously unexplored aspects of disease pathogenesis of this significant mycobacterial species.

这偶然分枝杆菌复合物包括几个密切相关的物种，导致肺部和肺外感染。然而，对所涉及的疾病发病机制的了解非常有限。M. 偶然感染，特别是由于缺乏合适的动物模型。使用斑马鱼模型，我们表明胚胎易受M. 偶然以剂量依赖的方式感染。此外，斑马鱼胚胎早在感染后 2 天就形成肉芽肿，概括了在其他致病物种中观察到的分枝杆菌发病机制的关键方面。受感染胚胎中细胞外索的形成突出了以前未知的致病特征M. 偶然. 大型绳状结构的形成也发生在体外增长，表明这不是感染期间部署的宿主适应压力机制。此外，短暂的巨噬细胞耗竭导致胚胎快速死亡，细胞外索增加，这表明巨噬细胞是M. 偶然感染控制。重要的是，囊性纤维化跨膜电导调节剂的吗啉代耗竭（cftr) 显着增加胚胎死亡、细菌负担、细菌索和脓肿。人数明显减少cftr- 与受感染的对照相比，具有肉芽肿的受感染胚胎缺陷，表明 CFTR 的丧失导致宿主免疫反应受损并赋予对M. 偶然感染。总的来说，这些发现突出了斑马鱼胚胎在研究中的应用M. 偶然并强调了这种重要分枝杆菌物种的疾病发病机制以前未探索的方面。