A recent breakthrough at the Research Institute of the McGill University Health Centre (RI-MUHC) could provide the answer to killing the “unkillable”: drug resistant bacteria. Published on September 10, 2018 in the Proceedings of the National Academy of Sciences of the United States of America, Dr. Dao Nguyen, an associate professor at McGill University and a scientist in the Respiratory Diseases Program at the RI-MUHC believes she has “identified a new function important to antibiotic tolerance, which could be targeted to enhance the activity of our current antibiotics” (1). Dr. Nguyen and her team discovered a cellular target in the bacterium Pseudomonas aeruginosa, which is highly tolerant to antibiotics and is the leading cause of death for people living with cystic fibrosis. This bacterial strain causes lifelong infections that no mix of available antibiotics can cure, so the repercussions of this research are incredibly powerful for medical professionals everywhere.
P. aeruginosa is listed along the “nightmare bacteria” by the Centers for Disease Control and Prevention in the U.S, causing 51,000 healthcare-associated infections- such as, pneumonia, bloodstream and urinary infections, and surgical site infections- each year, resulting in 400 deaths. But why? Dr. Nguyen attributes this to the fact that bacterium that enter metabolic quiescence, i.e. slow or no growth at all, become tolerant to antibiotics, which then translates to resistance in chronic infections or in relapse infections in patients. Interestingly, yet unfortunate for medical professionals, antibiotic tolerance can occur even when the infectious organism have no genetic resistance to the antibiotic (2). Such characteristic makes many chronic infections difficult to stop. The issue with this, is that the bacteria can then pass this tolerance and resistance down to their progeny, thus creating a huge concern for those in public health.
Given such, Dr. Nguyen targeted enzymes involved in the P. aeruginosa defense system in her team’s most current research. In studying the defense enzyme, superoxide dismutase, Nguyen and her team found a link between stress, defensive signalling and membrane permeability: when the bacterium either lacks nutrients or is under stress, like in a situation of antibiotic therapy, this defense enzyme triggers modifications in its cell membrane to make it less permeable, thus hindering the entrance of antibiotics into the cell. This research found that inhibiting superoxide dismutase activity could allow for more response to antibiotics, as the cell membrane would be more permeable.
It was previously believed that the intolerance in dormant and slow growing bacteria was due to the fact that this class of bacteria lacked a target all together. However, this link between stress defense enzymes, membrane permeability and antibiotic tolerance could prove very promising. Although just the beginning, Dr. Nguyen remarks that “in the long run, the discovery of this promising cellular target could expand the utility of our antibiotics and make new ones more effective” (1). If Nguyen could find this target in this bacteria commonly associated with lung infections, maybe there is a chance the same principles could be applied to other normally dormant or quiescent bacterium.
1. McGill University Health Centre. “New means to fight ‘unkillable’ bacteria in healthcare settings: Canadian scientists identify new cellular target to weaken P. aeruginosa — a severe threat to patients with cystic fibrosis.” ScienceDaily. ScienceDaily, 13 September 2018.
2. Martins, Dorival, et al. “Superoxide Dismutase Activity Confers (p)PpGpp-Mediated Antibiotic Tolerance to Stationary-Phase Pseudomonas Aeruginosa.” PNAS, 5 Sept. 2018, www.pnas.org/content/early/2018/09/04/1804525115.full.