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J. Bacteriol. doi:10.1128/JB.00741-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Structure and biological activities of beta-toxin from Staphylococcus aureus

Departments of Biochemistry, Molecular Biology and Biophysics and Microbiology, University of Minnesota, Minneapolis MN; Department of Microbiology, Molecular Biology and Biochemistry, University of Idaho, Moscow ID

^* To whom correspondence should be addressed. Email: Earhart{at}umn.edu.

	Abstract

Beta-toxin is a neutral sphingomyelinase secreted by certain strains of Staphylococcus aureus. This virulence factor lyses erythrocytes in order to evade the host immune system as well as scavenge nutrients. The structure of beta-toxin was determined to 2.4 Å resolution from crystals that were merohedrally twinned. Its structure is similar to the sphingomyelinases of Listeria ivanovii and Bacillus cereus. Beta-toxin belongs to the DNAse I folding superfamily; in addition to sphingomyelinases, the proteins most structurally related to beta-toxin include human endonuclease HAP1, Escherichia coli endonuclease III, bovine pancreatic DNAse I, and the endonuclease domain of TRAS1 from Bombyx mori. Our biological assays have demonstrated for the first time that beta-toxin kills proliferating human lymphocytes. Structure-directed active site mutations show that biological activities, including hemolysis and lymphotoxicity, are due to the sphingomyelinase activity of the enzyme.