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Infection and Immunity, July 2002, p. 3904-3914, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3904-3914.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Streptococcus-Zebrafish Model of Bacterial Pathogenesis

Melody N. Neely,^1, John D. Pfeifer,² and Michael Caparon^1*

Department of Molecular Microbiology, Washington University School of Medicine,¹ L. V. Ackerman Laboratory of Surgical Pathology, Washington University Medical Center, St. Louis, Missouri 63110-1093²

Received 10 December 2001/ Returned for modification 14 March 2002/ Accepted 27 March 2002

Due to its small size, rapid generation time, powerful genetic systems, and genomic resources, the zebrafish has emerged as an important model of vertebrate development and human disease. Its well-developed adaptive and innate cellular immune systems make the zebrafish an ideal model for the study of infectious diseases. With a natural and important pathogen of fish, Streptococcus iniae, we have established a streptococcus- zebrafish model of bacterial pathogenesis. Following injection into the dorsal muscle, zebrafish developed a lethal infection, with a 50% lethal dose of 10³ CFU, and died within 2 to 3 days. The pathogenesis of infection resembled that of S. iniae in farmed fish populations and that of several important human streptococcal diseases and was characterized by an initial focal necrotic lesion that rapidly progressed to invasion of the pathogen into all major organ systems, including the brain. Zebrafish were also susceptible to infection by the human pathogen Streptococcus pyogenes. However, disease was characterized by a marked absence of inflammation, large numbers of extracellular streptococci in the dorsal muscle, and extensive myonecrosis that occurred far in advance of any systemic invasion. The genetic systems available for streptococci, including a novel method of mutagenesis which targets genes whose products are exported, were used to identify several mutants attenuated for virulence in zebrafish. This combination of a genetically amenable pathogen with a well-defined vertebrate host makes the streptococcus-zebrafish model of bacterial pathogenesis a powerful model for analysis of infectious disease.

Editor: E. I. Tuomanen

Present address: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201.

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