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Infection and Immunity, November 2004, p. 6306-6312, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6306-6312.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Mycobacterium marinum Strains Can Be Divided into Two Distinct Types Based on Genetic Diversity and Virulence

Astrid M. van der Sar,1* Abdallah M. Abdallah,1 Marion Sparrius,1 Erik Reinders,1 Christina M. J. E. Vandenbroucke-Grauls,1,2 and Wilbert Bitter1

Department of Medical Microbiology and Infection Control, Vrije Universiteit Medical Centre,1 Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands2

Received 26 April 2004/ Returned for modification 3 June 2004/ Accepted 27 July 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.

* Corresponding author. Mailing address: Dept. Medical Microbiology, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. Phone: (31) 20 4448680. Fax: (31) 20 4448318. E-mail: a.vandersar{at}vumc.nl.

Editor: S. H. E. Kaufmann

Infection and Immunity, November 2004, p. 6306-6312, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6306-6312.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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