van der Sar Astrid M, Abdallah Abdallah M, Sparrius Marion, Reinders Erik, Vandenbroucke-Grauls Christina M J E, Bitter Wilbert
Department of Medical Microbiology and Infection Control, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands.
Infect Immun. 2004 Nov;72(11):6306-12. doi: 10.1128/IAI.72.11.6306-6312.2004.
Mycobacterium marinum causes a systemic tuberculosis-like disease in a large number of poikilothermic animals and is used as a model for mycobacterial pathogenesis. In the present study, we infected zebra fish (Danio rerio) with different strains of M. marinum to determine the variation in pathogenicity. Depending on the M. marinum isolate, the fish developed an acute or chronic disease. Acute disease was characterized by uncontrolled growth of the pathogen and death of all animals within 16 days, whereas chronic disease was characterized by granuloma formation in different organs and survival of the animals for at least 4 to 8 weeks. Genetic analysis of the isolates by amplified fragment length polymorphism showed that M. marinum strains could be divided in two clusters. Cluster I contained predominantly strains isolated from humans with fish tank granuloma, whereas the majority of the cluster II strains were isolated from poikilothermic species. Acute disease progression was noted only with strains belonging to cluster I, whereas all chronic-disease-causing isolates belonged to cluster II. This difference in virulence was also observed in vitro: cluster I isolate Mma20 was able to infect and survive more efficiently in the human macrophage THP-1 and the carp leukocyte CLC cell lines than was the cluster II isolate Mma11. We conclude that strain characteristics play an important role in the pathogenicity of M. marinum. In addition, the correlation between genetic variation and host origin suggests that cluster I isolates are more pathogenic for humans.
海分枝杆菌可在大量变温动物中引发一种类似系统性结核病的疾病,并且被用作分枝杆菌致病机制的模型。在本研究中,我们用不同菌株的海分枝杆菌感染斑马鱼(Danio rerio),以确定其致病性的差异。根据所分离的海分枝杆菌菌株不同,鱼类会患上急性或慢性疾病。急性疾病的特征是病原体不受控制地生长,所有动物在16天内死亡,而慢性疾病的特征是在不同器官形成肉芽肿,动物存活至少4至8周。通过扩增片段长度多态性对分离株进行基因分析表明,海分枝杆菌菌株可分为两个簇。簇I主要包含从患有鱼缸肉芽肿的人类中分离出的菌株,而簇II的大多数菌株是从变温动物物种中分离出来的。仅在属于簇I的菌株中观察到急性疾病进展,而所有导致慢性疾病的分离株都属于簇II。在体外也观察到了这种毒力差异:簇I分离株Mma20比簇II分离株Mma11能够更有效地在人类巨噬细胞THP-1和鲤鱼白细胞CLC细胞系中感染并存活。我们得出结论,菌株特征在海分枝杆菌的致病性中起重要作用。此外,基因变异与宿主来源之间的相关性表明,簇I分离株对人类的致病性更强。