A University of Alberta research team has identified a new drug target to treat harmful E. coli bacteria - which cause nearly 250,000 deaths a year from urinary tract infections (UTI) and are becoming increasingly resistant to antibiotics.
Recently published research in Nature Communications shows how the protease known as GlpG, located in the cellular membrane, is central to the bacteria's ability to infect human cells and resist treatment.
"This protease in pathogenic E. coli is essential for the formation of virulence factors known as pili, little hair-like appendages that sit on the bacterial surface and help the bacteria adhere to tissues," explains principal investigator Joanne Lemieux, professor of biochemistry and vice-dean of research for the Faculty of Medicine & Dentistry. "It 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."
The team showed that when they inhibited GlpG protease in pathogenic E. coli, they prevented bacterial adhesion and invasion into bladder and kidney cells. It stopped the formation of protective biofilms and eradicated biofilms that had started to form.
Lemieux's lab is now focused on developing new drugs that will inhibit the protease in pathogenic E. coli while leaving helpful E. coli in the gut untouched.
The global death rate due to UTIs increased by 140 per cent between 1990 and 2019 largely because of the rise of resistance to classes of commonly prescribed antibiotics.
Lemieux says antimicrobial resistance is now a global emergency.
"It's anticipated that by 2050, deaths due to antimicrobial resistance will equal those due to cancer," Lemieux says, noting the World Health Organization has listed E. coli as a pathogen of critical concern.
