Isolation and functional analysis of phage display-derived scFv-antibodies targeting the S. aureus SSLs
Sandberg, Rebecca (2020)
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Staphylococcus aureus is one of the leading causes of antibiotic resistant infections in the world today. In addition to its remarkable ability to acquire resistance to antibiotics, it is also successful at suppressing the host immune defense. S. aureus secretes an arsenal of virulence factors that in various ways help the bacteria escape the immune system. Staphylococcal superantigen-like protein 1 (SSL1), SSL5 and SSL10 are three proteins that the bacteria produces for this purpose. In this thesis, our goal was to generate single-chain variable fragments (scFvs) that bind and inhibit the immune evasion functions of these three SSLs. Using the phage display technique, we produced different scFvs that showed binding to SSL1, SSL5 and SSL10 in an ELISA screening assay. In functional analyses, the SSL1-binding scFv-93 showed the most promise. Previous research has revealed that SSL1 inhibits several matrix metalloproteinases (MMPs). ScFv-93 was able to recover over 90% of SSL1-inhibited MMP9 activity in a fluorogenic peptide MMP activity assay. Our results indicate that by binding to SSL1, scFv-93 is able to prevent SSL1 from inhibiting MMP9. These findings might in the future help understand the mechanisms of S. aureus immune evasion and be a starting point for developing new therapeutics for S. aureus infections.