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PMID: 12228303 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Identification of a streptolysin S-associated gene cluster and its role in the pathogenesis of Streptococcus iniae disease.

Infection and immunity ·Vol. 70 ·No. 10 ·2002-10-00 ·Pages 5730-9

Fuller JD, Camus AC, Duncan CL, Nizet V, Bast DJ, Thune RL, Low DE, De Azavedo JC

Abstract

Streptococcus iniae causes meningoencephalitis and death in cultured fish species and soft-tissue infection in humans. We recently reported that S. iniae is responsible for local tissue necrosis and bacteremia in a murine subcutaneous infection model. The ability to cause bacteremia in this model is associated with a genetic profile unique to strains responsible for disease in fish and humans (J. D. Fuller, D. J. Bast, V. Nizet, D. E. Low, and J. C. S. de Azavedo, Infect. Immun. 69:1994-2000, 2001). S. iniae produces a cytolysin that confers a hemolytic phenotype on blood agar media. In this study, we characterized the genomic region responsible for S. iniae cytolysin production and assessed its contribution to virulence. Transposon (Tn917) mutant libraries of commensal and disease-associated S. iniae strains were generated and screened for loss of hemolytic activity. Analysis of two nonhemolytic mutants identified a chromosomal locus comprising 9 genes with 73% homology to the group A streptococcus (GAS) sag operon for streptolysin S (SLS) biosynthesis. Confirmation that the S. iniae cytolysin is a functional homologue of SLS was achieved by PCR ligation mutagenesis, complementation of an SLS-negative GAS mutant, and use of the SLS inhibitor trypan blue. SLS-negative sagB mutants were compared to their wild-type S. iniae parent strains in the murine model and in human whole-blood killing assays. These studies demonstrated that S. iniae SLS expression is required for local tissue necrosis but does not contribute to the establishment of bacteremia or to resistance to phagocytic clearance.

MeSH Terms
Amino Acid Sequence Animals Bacterial Proteins Base Sequence Chromosome Mapping DNA, Bacterial/genetics Disease Models, Animal Female Fishes Gene Expression Genes, Bacterial Hemolysis/genetics Humans Mice Molecular Sequence Data Multigene Family Mutagenesis, Insertional Phagocytosis Sequence Homology, Amino Acid Streptococcal Infections/etiology Streptococcus/genetics,immunology,pathogenicity Streptolysins/genetics Virulence/genetics
Chemicals
Bacterial Proteins DNA, Bacterial Streptolysins streptolysin S
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Fuller Jeffrey D
Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada.
Camus Alvin C
Duncan Carla L
Nizet Victor
Bast Darrin J
Thune Ronald L
Low Donald E
De Azavedo Joyce C S
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.70.10.5730-5739.2002
Published
2002-10-00
Pages
5730-9
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC128303
Subset
IM
Databases
GENBANK
AF465842
External Links
PubMed source DOI: 10.1128/IAI.70.10.5730-5739.2002 PMC Full Text View journal details
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