Innate Defence Regulator Peptides as a Novel Anti-infective Strategy (94.2)

Abstract

Abstract The therapy of bacterial infections is under great threat as multiple antibiotic resistance increases and there is a paucity of new antibiotic discovery and development. Synthetic Innate Defence Regulator (IDR) peptides, which mimic natural host defence (antimicrobial) peptides, have been designed as a novel anti-infective strategy, working by selectively boosting innate immune protective mechanisms while dampening potentially harmful inflammation. These peptides can resolve serious infections in animal models. The optimal method of use of these peptides was evaluated here using an animal model infection by one of the highly resistant bacteria (Superbugs) afflicting our society, Staphylococcus aureus. A luminescent version of this bacterium was utilized to follow the kinetics of infection non-invasively using IVIS imaging. Protection was achieved by both prophylactic and therapeutic administration. Investigation of the mechanism of protection by examining cells infiltrating the infection site and cytokines/chemokines revealed remarkable parallels between in vitro action of the peptides in primary human cells and these animal models. System biology approaches such as Microarray and InnateDB are being utilized to decipher the complex. This has revealed several receptors, signaling pathways, transcription factors and effector proteins involved in the modulation by peptides of innate immunity.