Targeted amino acid substitutions impair streptolysin O toxicity and group A Streptococcus virulence.

ABSTRACT:

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Streptolysin O is a potent pore-forming toxin produced by group A Streptococcus. The aims of the present study were to dissect the relative contributions of different structural domains of the protein to hemolytic activity, to obtain a detoxified form of streptolysin O amenable to human vaccine formulation, and to investigate the role of streptolysin O-specific antibodies in protection against group A Streptococcus infection. On the basis of in silico structural predictions, we introduced two amino acid substitutions, one in the proline-rich domain 1 and the other in the conserved undecapeptide loop in domain 4. The resulting streptolysin O derivative showed no toxicity, was highly impaired in binding to eukaryotic cells, and was unable to form organized oligomeric struc

SUBMITTER: Chiarot E 

PROVIDER: S-EPMC3546560 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature