UCLA researchers discover nanomachine that recognizes and kills bad bacteria

Researchers at UCLA have discovered a nanomachine that could work like an antibiotic, recognizing and killing bacteria. The team published their study in Nature on April 15.  

The nanomachine that researchers Peng Ge, Dean Scholl, Nikolai S. Prokhorov, Jaycob Avaylon, Christopher Browning, Mikhail M. Shneider, Sergey A. Buth, Urmi Chakraborty, Michel Plattner, Ke Ding, Petr G. Leiman, Jeff F. Miller, and Z. Hong Zhou explored is known as an R-type pyocin.

The Pseudomonas aeruginosa bacterium releases this protein complex to punch a hole in the membrane of other cells that it senses are competition. P. aeruginosa is often found in soil, water, and on fresh produce. It is also a common cause of hospital-acquired illness. The team examined the pyocin’s structure before it attacked the offending bacterium and after, which helped them to understand how it works.

“If you tried to design a pyocin from scratch, you probably couldn’t do it,” said Z. Hong Zhou, the study’s co-corresponding author and the faculty director of the Electron Imaging Center for Nanomachines at the California NanoSystems Institute at UCLA. “It’s good to learn from nature, because nature has developed and tested these systems over billions of years. That should help us from an engineering standpoint.”

Using X-ray crystallography and cryo-electron microscopy, the team was able to see the structure of the frozen pyocin cells in more detail. They discovered a six-stranded collar at the top of the pyocin which helps to transmit energy as the pyocin is triggered. They also noted that the outer sheath of the pyocin collapses around the offending bacterium and the inner tube attacks the target cell, which also leaches energy from that cell and kills it.

“This is a mechanical system that’s exquisitely tuned to couple specific recognition of a target cell with deployment of its lethal blow,” said co-corresponding author Jeff F. Miller, UCLA’s Fred Kavli Professor of NanoSystems Sciences and the director of CNSI. “Understanding how the system is constructed and how its activity is controlled could be used for building new kinds of nanomachines.”

The National Institutes of Health, the Swiss National Scientific Foundation, and the Kavli Foundation supported this research.