Here's how mysterious last-resort antibiotics kill bacteria – Science News Magazine

Support nonprofit journalism.
Polymyxin “last-resort” antibiotics kill bacteria by crystallizing their cell membranes.
Ted Horowitz/The Image Bank/Getty Images

To kill drug-resistant bacteria, “last-resort” antibiotics borrow a tactic from Medusa’s playbook: petrification.
New high-resolution microscope images show that a class of antibiotics called polymyxins crystallize the cell membranes of bacteria. The honeycomb-shaped crystals that form turn the microbes’ usually supple skins of fat molecules into thin brittle sheets, researchers report October 21 in Nature Communications. When the petrified membranes break, the bacteria die.
The finding was a total surprise, says Sebastian Hiller, a structural biologist at the University of Basel in Switzerland.
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.
In the new study, Hiller and colleagues exposed bits of cell membrane from Escherichia 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.”
How exactly polymyxins crystallize cell membranes remains unclear. That’s a problem because some bacteria have developed resistance to polymyxins and are becoming 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.
Subscribe to Science News to satisfy your omnivorous appetite for universal knowledge.
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.
Questions or comments on this article? E-mail us at [email protected]
S. Manioğlu et al. Antibiotic polymyxin arranges lipopolysaccharide into crystalline structures to solidify the bacterial membrane. Nature Communications. Published online October 21, 2022. doi: 10.1038/s41467-022-33838-0.
Science News produces award-winning journalism, and Society for Science, our parent organization, provides programs to make sure that every young person can strive to become an engineer or scientist. Make a gift today to support all we do, including our outreach and equity STEM Programs and world-class science research competitions.
Science News was founded in 1921 as an independent, nonprofit source of accurate information on the latest news of science, medicine and technology. Today, our mission remains the same: to empower people to evaluate the news and the world around them. It is published by the Society for Science, a nonprofit 501(c)(3) membership organization dedicated to public engagement in scientific research and education (EIN 53-0196483).
© Society for Science & the Public 2000–2022. All rights reserved.
Subscribers, enter your e-mail address for full access to the Science News archives and digital editions.
Not a subscriber?
Become one now.


Leave a Comment