NANONET-FORMING ANTIMICROBIAL PEPTIDE-BASED THERAPY AGAINST GRAM-NEGATIVE BACTERIA INFECTION

Abstract

Treatment of Gram-negative bacteria infections is faced with major challenges of antibiotic resistance and overactive host inflammatory responses. Therefore, antimicrobial therapeutics with multiple complementary functionalities are increasingly explored to offer more holistic anti-infective therapies. Although antimicrobial peptides (AMPs) have been extensively studied over recent decades as an alternative source of antimicrobial drugs, there has been a recent surge in appreciation of their multifunctionalities as immune defense components, including immunological modulation and physical entrapment of bacteria. Our lab previously designed a series of ?-hairpin peptides which displayed bacteria-responsive formation of antibacterial trap-and-kill nanonets. Building on the foundational works, the overarching goal of this thesis is to further expand the functional repertoire of these nanonet-forming AMPs (also termed as fibrillating peptides), to overcome the challenges of drug resistance and inflammatory disorders occurring in infections caused by Gram-negative bacteria, while improving their clinical profiles.