title: Streptococcus iniae beta-hemolysin streptolysin S is a virulence factor in fish infection.
abstract: Streptococcus iniae is a leading pathogen of intensive aquaculture operations worldwide, although understanding of virulence mechanisms of this pathogen in fish is lacking. S. iniae possesses a homolog of streptolysin S (SLS), a secreted, pore-forming cytotoxin that is a proven virulence factor in the human pathogen S. pyogenes. Here we used allelic exchange mutagenesis of the structural gene for the S. iniae SLS precursor (sagA) to examine the role of SLS in S. iniae pathogenicity using in vitro and in vivo models. The isogenic Delta sagA mutant was less cytotoxic to fish blood cells and cultured epithelial cells, but comparable to wild-type (WT) S. iniae in adherence/invasion of epithelial cell monolayers and resisting phagocytic killing by fish whole blood or macrophages. In a hybrid striped bass infection model, loss of SLS production led to marked virulence attenuation, as injection of the Delta sagA mutant at 1000x the WT lethal dose (LD80) produced only 10% mortality. The neutralization of SLS could represent a novel strategy for control of S. iniae infection in aquaculture.
authors: Department of Pediatrics, Division of Pharmacology & Drug Discovery, University of California, San Diego, 9500 Gilman Drive, MC 0687, La Jolla, California 92093-0687, USA.
authors: Jeffrey B
authors: JB
authors: Locke
authors: Kelly M
authors: KM
authors: Colvin
authors: Nissi
authors: N
authors: Varki
authors: Mike R
authors: MR
authors: Vicknair
authors: Victor
authors: V
authors: Nizet
authors: John T
authors: JT
authors: Buchanan
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics*; D001492:Bass / Q000382:microbiology; D001921:Brain / Q000382:microbiology / Q000473:pathology; D002347:Carps / Q000382:microbiology; D002460:Cell Line; D015169:Colony Count, Microbial; D005393:Fish Diseases / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial; D005818:Genetic Engineering / Q000662:veterinary; D006461:Hemolysis; D053208:Kaplan-Meier Estimate; D009154:Mutation; D013290:Streptococcal Infections / Q000382:microbiology / Q000662:veterinary*; D013291:Streptococcus / Q000235:genetics / Q000472:pathogenicity*; D013301:Streptolysins / Q000096:biosynthesis / Q000235:genetics*; D013997:Time Factors; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics* / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D013301:Streptolysins; D037521:Virulence Factors; C026050:streptolysin S