Development of a broad spectrum antimicrobial to combat chronic lung infection

Project Summary Bacterial resistance has reached alarming levels in the US and other parts of the world in the past decade. The increase in bacterial infection with antimicrobial resistant (AMR) pathogens are resulting in increasing healthcare costs and a decline in positive clinical outcomes. According to the Center for Disease Control’s Antibiotic Resistance Threats in the United States 2019 report (2019 AR Threats Report), more than 2.8 million antibiotic- resistant infections occur in the U.S. each year, and more than 35,000 people die as a result. New therapies for controlling these AMR pathogen-induced infections are urgently needed because: (a) the mortality rate among infected individuals requiring hospitalization remains very high; and (b) overuse of antibiotics has resulted in continuing emergence of additional multi-drug resistant (MDR) strains. There is a dire need to develop novel antimicrobial compounds that have a broad spectrum of activity against AMR bacteria that are both well tolerated and have a low propensity to select for resistant strains of bacteria. Our long-term goal is to develop an effective, safe therapeutic to MDR pathogens determined to be critical and high priority by the CDC and the World Health Organization (WHO). We seek to develop our lead antimicrobial peptide, CM-YPD1, with broad-spectrum activity against clinical isolates of ESKAPE pathogens to treat the growing number of patients with MDR infections. This proposal focuses on development of CM-YPD1 for treatment of chronic lung infection in cystic fibrosis patients. Our multidisciplinary team brings together a unique combination of academic and commercial expertise that will permit the development of a drug that can be used to treat the growing number of patients with life-threatening MDR bacterial infections.