INACTIVATION OF BACTERIAL PATHOGENS--S AUREUS

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This grant proposes to produce selenium labelled peptides and phage (bacterial viruses) that can selectively bind to the surface of pathogenic bacteria and inactivate them through the generation of superoxide radicals on their surface. For the purposes of this grant we will develop these labelled seleno- peptides and phage (from display libraries) against the bacteria Staphylococcus aureus. This proposal is based upon technology that has been found to be extremely selective and potent against pathogens. These seleno-peptides and selenium labelled phage should provide a safe means for instant protection from Staphylococcus aureus before it can cause damage. In addition, this approach utilizes a technology for which bacteria should not be able to become resistant since the superoxide radical killing of bacteria is lymphocytic mechanism that is used by the macrophage. The present grant proposal will: 1) select specific peptides and phage that bind selectively to the surface of Staphylococcus aureus; 2) increase the affinity and specificity of these specific peptides and phage by computer assisted evolution; 3) synthesize selenium labelled peptides and phage; and 4) test the ability of these selenium labelled peptides and phage to inactivate Staphylococcus aureus in vitro and in vivo.