University of Alberta Team Identifies New Drug Target for Antibiotic-Resistant E. coli
University of Alberta researchers have identified the protease GlpG as a new drug target for antibiotic-resistant E. coli, which causes hundreds of thousands of UTI deaths annually. Inhibiting GlpG prevented bacterial adhesion and biofilm formation in laboratory studies. The discovery addresses a global health emergency as antimicrobial resistance projections show it could cause cancer-level deaths by 2050.
University of Alberta researchers have identified a new drug target to combat antibiotic-resistant E. coli bacteria, which cause nearly 250,000 deaths annually from urinary tract infections. The research, published in Nature Communications, reveals that the protease GlpG, located in the cellular membrane, is central to the bacteria's ability to infect human cells and resist treatment.
Principal investigator Joanne Lemieux, professor of biochemistry and vice-dean of research for the Faculty of Medicine & Dentistry, explained that GlpG is essential for the formation of virulence factors known as pili—hair-like appendages on the bacterial surface that help adhere to tissues. The protease also plays a key role in the formation of biofilms that protect bacteria from the immune system and antibiotics, leading to persistent and chronic infection. When the team inhibited GlpG in pathogenic E. coli, they prevented bacterial adhesion and invasion into bladder and kidney cells, stopped the formation of protective biofilms, and eradicated biofilms that had already formed. The lab is now focused on developing new drugs that will inhibit this protease in pathogenic E. coli while leaving helpful E. coli in the gut untouched.
The global death rate due to urinary tract infections increased by 140 percent between 1990 and 2019, largely because of the rise of resistance to commonly prescribed antibiotics. Lemieux described antimicrobial resistance as a global emergency, noting that the World Health Organization has listed E. coli as a pathogen of critical concern. It is anticipated that by 2050, deaths due to antimicrobial resistance will equal those due to cancer. Up to one-fifth of E. coli infections are already resistant to antibiotics.
Protease inhibitors are already in use as medications to treat other diseases such as blood disorders, HIV, and COVID-19. The research team collaborated with colleagues from biochemistry, medical microbiology, and pediatrics. Funding came from the Canada Foundation for Innovation, the Natural Sciences and Engineering Research Council of Canada, the Alberta Graduate Excellence Scholarship, the Stollery Children’s Hospital Foundation, and the Alberta Women’s Health Foundation through the Women and Children’s Health Research Institute and Striving for Pandemic Preparedness – The Alberta Research Consortium.