Small molecules for bad bacteria: Novel peptidomimetics to battle resilient clinical infections

The lack of effective antibiotics in cases such as surgeries, transplantations, early-term and complicated births, sepsis etc. could merely lead to death as antibiotics are crucially needed for treatment. Sepsis for instance, annually kills ~8 million people worldwide with almost 40% of all deaths are linked to antibiotic failure. Likewise, infections caused by bacterial biofilms represent ~65% of all clinical diseases, and there are no antibiotics to treat bacterial biofilms, specifically. Here, we propose using new synthetic and biosynthetic technologies to develop novel molecules alternative to antibiotics, particularly antimicrobial peptide-like compounds, to address a wide range of hard-to-treat bacterial infections.

Starting from our previously developed immunomodulatory and antibiofilm peptides, we aim to explore the structure-activity relationships of those peptides and biosynthetically design stable and highly active mimetics. We plan to use advanced animal models, synthetic and isolated human tissues (skin and lung tissues) for testing and addressing preclinical issues such as stabilities, formulations, toxicities, and optimal therapeutic dosing. If successful the proposed study will provide the first novel therapeutic strategy to tackle bacterial infections and these newly developed compounds would have a significant impact in treating diseases and preventing deaths.