Yale scientists take the driving seat in pursuit of Lyme disease answers

The Cryo-EM reveals the 3D model that helped Yale scientists understand the rotational switching in the Lyme disease spirochete.

Scientists at Yale have unlocked a 50-year puzzle of how certain bacteria spread harmful disease.

Published today in Nature Structural & Molecular Biology, scholars from the Yale Microbial Sciences Institute provide a major new insight to the corkscrew-shaped bacterium – or spirochete - that causes Lyme disease.

Spirochetes are like biological smart cars – burrowing into tissues, nerves and joints with the aid of a tiny molecular motor with gear-like switches for forward and reverse navigation.

Understanding this motor is critical to understanding how the spirochete controls its unique motility, but so far scientists have been unable to dissect the mechanism at a molecular level.

“We were able to reveal the direct interactions between a signaling protein and the switch proteins that control the rotational switching in the Lyme disease spirochete for the first time through the lens of a cryo-electron microscope (cryo-EM),” explained the study’s first author, Yunjie Chang, a postdoc in the lab of Jun Liu at the university’s West Campus.

The cryo-EM technique flash-freezes bacterial cells to around -270°F then bombards them with electrons to produce thousands of 2D images, which are then stitched together to reveal a 3D model and the structural basis to understand the rotational switching.

“This microscope is key,” said senior author Jun Liu, associate professor of Microbial Pathogenesis. “The power allows us to see through the Lyme disease vehicle, to understand how it navigates and disseminates in its hosts, and how in the future we can control it.”

The Centers for Disease Control and Prevention estimate that 300,000 people get Lyme disease in the US every year.

By Jon Atherton