Designing selective peptide binders for Methicillin resistance Staphylococcus aureus

The growing global crisis of antibiotic resistance highlights the need for novel approaches in diagnosing and treating bacterial infections.Methicillin-resistant Staphylococcus aureus (MRSA) presents a particularly severe threat, especially in healthcare environments.This study aims to advance the development of rapid and selective peptide binders for MRSA as a model bacterium.Peptides, with their potential for modification and cost-effectiveness, offer significant promise for creating effective bacterial binders.We employed phage display technology to identify unique peptide binders with high affinity for MRSA cells.This method involved using whole bacterial cells in suspension during the assay, which increased the diversity of the selection process.During the phage display screening, the peptide library was exposed to various types of bacteria (negative selection) to enhance selectivity towards MRSA (the target bacteria).Subsequent Next Generation Sequencing and bioinformatics analysis allowed us to select sequences that were present in high abundance in the MRSA treatment compared to the negative selection bacterial cells.The identified lead peptides were synthesized, purified, and characterized using two methods: Flow Cytometry for suspension-based interactions and gold surface immobilization for interactions on surfaces.The lead peptides demonstrated strong binding affinities for MRSA in both immobilized and suspension conditions, with promising specificity.Chemical modifications further enhanced the binding affinities, resulting in peptides that showed even greater affinity for MRSA than the original sequences.Notably, the two leading peptide binders, WPG and TST, along with the modified peptide WPG11A, exhibited high selectivity for MRSA, even in mixed bacterial populations.Importantly, these peptides showed no toxicity towards either bacterial or mammalian cells, highlighting their potential for safe application in diagnostic and therapeutic settings.Our study successfully identifies selective peptide binders for MRSA using innovative phage display technology.The characterized peptides demonstrate promising selectivity and high binding affinity for MRSA, laying the basis for the development of rapid and specific bacteria detection technologies.