Antimicrobial peptides to combat MDR ESKAPE pathogens

Project Summary Bacterial resistance has reached alarming levels in the US and other parts of the world in the past decadeThe increase in bacterial infection with drug resistantDRpathogens are resulting in increasing healthcare costs and a decline in positive clinical outcomesSerious infections leading to sepsis remain a public health concernIn the United States aloneapproximatelypatients develop sepsiswhich claimslives every year with treatment failures often associated with multidrug resistanceMDRbacterial pathogens as well as the complex pathophysiology of the diseaseNew therapies for controlling these DR pathogen induced respiratory infections are urgently needed becauseathe mortality rate among infected individuals requiring hospitalization remains very highandboveruse of antibiotics has resulted in continuing emergence of additional MDR strainsOur long term goal is to develop an effectivewell tolerated antimicrobial peptide therapeutic to MDR pathogensspecifically the MDR Enterococcus faeciumStaphylococcus aureusKlebsiella pneumoniaeAcinetobacter baumanniiPseudomonas aeruginosa and Enterobacter sppESKAPEpathogens determined to be critical and high priority by the CDC and WHOThere is thus a dire need to develop novel antimicrobial compounds that have a broad spectrum of activity against both Gram positive and Gram negative bacteriayet at the same timeare well tolerated with a low propensity to select for resistant strains of bacteriaThis proposal seeks to develop computationally engineered synthetic antimicrobial peptides derived from a normal human protein with very low toxicity but broad spectrum activity against MDR clinical bacterial isolatesOur lead therapeuticCM YPDhas been validated in vitro and in vivo to have strong efficacystabilityand safety and acts within minutesOur multidisciplinary team brings together a unique combination of expertise and technology that will permit the development of a drug that can be used to treat a broad array of MDR bacterial infections Narrative Multi drug resistantMDRbacterial infections are becoming an increasing threat to human health and byexpected to be responsible for overMillion deaths per yearWe have discovered and optimized a promising new therapy to overcome MDR infectionsThe successful development of a potentsafe therapeutic able to combat a broad spectrum of MDR bacterial infections will be a transformative step in healtcare