Hamilton, ON – Combining two mutations in non-essential genes can lead to extreme antibiotic resistance in Pseudomonas aeruginosa, one of the leading causes of hospital-inquired infections.
These findings come from a new study published in the journal Antimicrobial Agents and Chemotherapy, led by Lori Burrows, McMaster biochemistry professor and member of the Michael G. DeGroote Institute for Infectious Disease Research and her trainees Joseph Cavallari and Ryan Lamers.
“Pseudomonas aeruginosa is an environmental bacterium that infects patients whose immune systems are compromised,” says Burrows. “It is already resistant to many common antibiotics and can easily become extremely resistant with only one or two mutations. In this paper, we found three different mutations that cause high-level resistance to beta lactam antibiotics (related to penicillin) that target bacterial cell wall synthesis. Combining two of the mutations leads to extreme resistance. The mutations lead to increased production of AmpC, an enzyme that degrades the antibiotics.”
They call the mutants “HARMs” (High-level-AmpC Resistant Mutants), Burrows says, adding the lab also discovered two mutations that make the bacteria more easily killed by beta lactams; those strains they, call “WIMPs” (Wall-Impaired Mutant Phenotypes).
“Both HARMs and WIMPs lack specific bacterial cell wall degrading enzymes, showing that the ultimate effect on antibiotic resistance depends on which enzyme is missing. Because of this effect, targeting this class of enzyme with novel drugs might increase beta-lactam susceptibility, but only if the drugs are specific for WIMPs,” she explains.
She adds this is the first time that inactivation of a single lytic transglycosylase (LT) has been linked to increased resistance.
Reported by Chantall Van Raay, McMaster University