Antimicrobial resistance is a growing global issue that threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses, and fungi. To avert this from happening, researchers have been hard at work to unearth solutions – before it’s too late.
Scientists at the Research Institute of the McGill University Health Centre (RI-MUHC) have discovered a new cellular target that can weaken the bacterium Pseudomonas aeruginosa, an intimidating microbe which can become highly tolerant to many antibiotics, and consequently refractory to antibiotic therapy. The team’s findings are published in Proceedings of the National Academy of Sciences (PNAS).
“We identified a new function important to antibiotic tolerance, which could be targeted to enhance the activity of our current antibiotics,” says lead study author Dr. Dao Nguyen, a scientist from the Translational Research in Respiratory Diseases Program at the RI-MUHC and an associate professor of Medicine at McGill University. “This is critical if we want to improve the efficacy of our antibiotics and prevent such treatments from failing.
“P. aeruginosa causes lifelong lung infections in individuals with cystic fibrosis, and these infections cannot be cleared, even by cocktails of the most potent antibiotics available.” – Dr. Nguyen
P. aeruginosa is a lung infection that severely impacts the health of people who have been diagnosed with cystic fibrosis. It is the leading cause of death for thousands patients, and causes many other serious infections to people with weakened immune systems.
“P. aeruginosa causes lifelong lung infections in individuals with cystic fibrosis, and these infections cannot be cleared, even by cocktails of the most potent antibiotics available,” says Dr. Nguyen, who is also a respirologist at the McGill University Health Centre.
The Centres for Disease Control and Prevention (CDC) in the United States has listed P. aeruginosa as one of the “nightmare bacteria”, with an impact of roughly 51,000 health care-associated infections each year that results in over 400 possibly preventable deaths. It is a common cause of pneumonia, surgical site infections, bloodstream or urinary tract infections.
“Many bacteria, such as P. aeruginosa, when they grow slowly or do not grow at all, become tolerant to antibiotics,” explains Dr. Nguyen. “This is a crucial problem because many chronic infections are caused by bacteria that are slow growing or enter a dormant state when they reside in a living host, and this causes treatments to fail or infections to relapse in patients.”
The recent discovery that Dr. Nguyen and her team exposed is that when P. aeruginosa is under stress or lacking nutrients it uses a stress signaling system and defense enzyme (superoxide dismutase) to modify its cell membrane, making it less permeable to molecules and preventing antibiotics from penetrating the cell.
The Centres for Disease Control and Prevention (CDC) in the United States has listed P. aeruginosa as one of the “nightmare bacteria”, with an impact of roughly 51,000 health care-associated infections each year that results in over 400 possibly preventable deaths.
The researchers thought that if they inhibit the enzyme activity or the stress signaling system, they could render the pathogen more susceptible to antibiotics; and as it turns out, they were right.
“Up until now antibiotic tolerance in slow-growing bacteria was widely attributed to the fact that targets of antibiotics were not available or inactive in ‘dormant’ cells. With this research we have shown there is more to it than that” explains Dr. Nguyen. “We identified a new link between the stress defense enzyme, the regulation of membrane permeability and antibiotic tolerance. In the long run, the discovery of this promising cellular target could expand the utility of our antibiotics and make new ones more effective.”
This research that Dr. Nguyen and her team have done may prove to be extremely valuable as the world progresses towards a more drug-resistant future. Without effective antibiotics, the world will be in peril, as treatments such an chemotherapy, invasive surgery, or even a small wound may be jeopardized. This threat requires immediate global action from all government sectors and society.