INACTIVATION OF BACTERIAL PATHOGENS--S AUREUS

这项拨款建议生产硒标记的多肽和噬菌体(细菌病毒)，这些多肽和噬菌体可以选择性地结合到病原体的表面，并通过在其表面产生超氧自由基来灭活它们。为了这笔赠款的目的，我们将开发这些标记的硒多肽和噬菌体(从展示文库中)来对抗金黄色葡萄球菌。这一建议是基于已被发现具有极高选择性和对病原体有效的技术。这些硒多肽和硒标记噬菌体应该提供了一种安全的手段，在金黄色葡萄球菌造成损害之前对其进行即时保护。此外，这种方法利用了一种细菌不应该能够产生抗药性的技术，因为超氧阴离子自由基杀死细菌是巨噬细胞使用的淋巴细胞机制。目前的拨款建议将：1)选择选择性结合在金黄色葡萄球菌表面的特定多肽和噬菌体；2)通过计算机辅助进化提高这些特定多肽和噬菌体的亲和力和特异性；3)合成硒标记的多肽和噬菌体；以及4)测试这些硒标记的多肽和噬菌体在体外和体内灭活金黄色葡萄球菌的能力。

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.