The hypermutability of one gene in Pseudomonas aeruginosa was found to drive resistance to colistin, a discovery that researchers said could help improve their understanding of superbugs’ resistance to the antibiotic as a last resort.
Natalia Chapel† doctorate, a researcher at the University of Oxford, and colleagues published the study in Cell reports.
Colistin is widely regarded as “an important last line of defense” against infections caused by multidrug-resistant (MDR) Gram-negative pathogens, and “there is an urgent need to understand how bacterial pathogens adapt to colistin treatment,” the researchers wrote.
Exposure to colistin causes rapid cell death in bacteria, according to the researchers, but some populations will eventually recover due to heteroresistant cell subpopulations. Because colistin resistance “remains poorly understood,” Kapel and colleagues analyzed about 1,000 populations of an (MDR) strain of P. aeruginosa and how they respond to high-dose colistin.
pseudomonas often causes lung infections in hospitalized patients, according to a press release about the study. The researchers wrote that it has moderate efficacy against: P. aeruginosa infections.
After treating the P. aeruginosa populations with colistin, Kapel and colleagues sequenced the genomes to analyze the genetic mutation that causes resistance and the rate at which different populations developed resistance.
The bacteria developed resistance “at a much faster rate than expected,” according to the release, but there was hope in the discovery that populations of pathogens “lost resistance quickly” once the antibiotic was removed due to its high mutation rate.
“Our work has shown that a gene involved in resistance to an antibiotic as a last resort mutates at an incredibly fast rate, allowing bacteria to rapidly develop antibiotic resistance,” Craig MacLeansaid a professor of evolution and microbiology at the University of Oxford in the release.
pseudomonas infections were able to quickly develop resistance due to a gene – pmrB – that mutates 1,000 times the norm.
“Our research suggests that, for this particular case, selective pressures generated by the association of this gene with the immune system may have driven the evolution of extra-fast mutation rates, which evolve rapidly to make bacteria resistant to antibiotics,” MacLean said in the late loose.