To kill drug-resistant bacteria, “last-resort” antibiotics borrow a tactic from Medusa’s playbook: petrification.
New high-resolution microscope photos show that polymyxins, an antibiotic class, crystallize cell membranes of bacteria. The honeycomb-shaped crystals that form turn the microbes’ usually supple skins of fat molecules into Thin, fragile sheetsResearchers report October 21 in Nature Communications. The bacteria dies when the petrified membranes are broken.
Sebastian Hiller, a structural biologist from the University of Basel, Switzerland, said that it was quite a surprise.
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.”
In the 1940s, polymyxin antibiotics such as colistin were first discovered. They are used today as a last-ditch defense against bacterias that have developed resistance to other drugs. Polymyxins interfere with the cell membranes of bacteria, which was known by researchers. But nobody had imagined a scenario like the “waffles” the team discovered.
Hiller and his colleagues revealed bits of cell membrane in a new study. Escherichia coliThere are many concentrations of colistin. The atomic force microscopy imaging revealed crystal formation at the lowest concentrations of colistin required to kill bacteria. Colistin-resistant strains exposed to the drug didn’t form crystals.
Polymyxins are known to cause cell membranes to crystallize, making them fragile 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.”
It’s not known how polymyxins crystallize cell-membrane membranes. That’s a problem because Some bacteria have shown resistance to polymyxinsThey are becoming increasingly popular More widespread (SN: 5/27/16; SN: 10/30/90). Without more studies like this one to help reveal how the drugs work, scientists can’t effectively modify the antibiotics to make them more effective, Weingarth says.
Hiller hopes that this first glimpse of polymyxins’ petrifying powers will help scientists combat resistance to the antibiotics.
“Understanding these concepts will definitely bring a lot of ideas — and the potential to make new drugs,” Hiller says.
