To kill drug-resistant bacteria, 'last-resort' antibiotics borrow a tactic from Medusa’s playbook: petrification.
Hiller, biophysicist Selen Manioğlu and their colleagues had been using the antibiotics as a control for a different experiment. When the researchers turned on their microscopes, “we saw these waffles,” Hiller says. “I immediately recognized, wow, this must be something special.”
Polymyxin antibiotics like colistin were discovered in the 1940s and are now used as a powerful last-ditch defense against bacteria that have evolved resistance to most other drugs. Researchers already knew that polymyxins somehow interfere with bacterial cell membranes. But nobody had imagined a scenario like the “waffles” the team discovered.
Bacterial cell membranes are usually supple and smooth, but polymyxin antibiotics crystallize the membranes into brittle sheets of hexagonal “waffles,” seen here in atomic force microscopy imagery.coli to varying concentrations of colistin. Imaging with atomic force microscopy revealed that crystals formed at the minimum concentrations required to kill the bacteria. Colistin-resistant strains exposed to the drug didn’t form crystals.
The results indicate that polymyxins work by arranging the cell membrane into a crystalline structure that leaves it brittle and vulnerable. “That’s something that has not even remotely been hypothesized so far,” says Markus Weingarth, a biochemist at Utrecht University in the Netherlands who was not involved in the work. “It’s a very important study. I’d even say it’s a breakthrough.”
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