Vanderbilt team shows how stomach bug can trigger cancer 7/16/19, 11(22 PM

DISEASE | CANCER

Vanderbilt team shows how stomach bug can

trigger cancer
BY LABLINE — JULY 16, 2019

Researchers at Vanderbilt University and the University of Michigan in Ann Arbor have obtained the
first high-resolution image of a molecular “machine” used by the insidious stomach bug Helicobacter
pylori (H. pylori) to inject a cancer-causing protein into the stomach lining.

Their report published recently in the journal eLife provides new insights into mechanisms by which
H. pylori can trigger the development of cancer.

In addition, “this study helps us understand why some H. pylori strains are more likely to cause
gastric cancer than other strains,” said Timothy Cover, MD, professor of Medicine and of Pathology,
Microbiology and Immunology in the Vanderbilt University School of Medicine.

Cover said his lab’s research was a “wonderful collaborative project” conducted in conjunction with
the labs of D. Borden Lacy, PhD, the Edward and Nancy Fody Professor of Pathology at Vanderbilt,
and Melanie Ohi, PhD, a former Vanderbilt faculty member now at the University of Michigan Life
Sciences Institute.

Bacterial pathogens have evolved elaborate strategies to infect their hosts. Some strains of H. pylori,
for example, contain a large chromosomal region known as a “pathogenicity island” that encodes
the bacterial oncoprotein CagA as well as components of an elaborate transmembrane complex
known as a type IV secretion system.

This mushroom
This mushroom-like molecular machine is required to inject CagA into stomach cells and is an
important step in the development of gastric cancer.

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Vanderbilt team shows how stomach bug can trigger cancer 7/16/19, 11(22 PM

People who are infected by CagA-injecting H. pylori strains are more likely to develop gastric cancer
or peptic ulcer disease than are people infected by other H. pylori strains that don’t have a
pathogenicity island and therefore can’t produce the “CagA injector.”

To visualize the secretion system, the researchers used single particle cryo-electron microscopy, a
technique performed at cryogenic temperatures (below minus 238 degrees Fahrenheit). The
technique bounces electrons o! proteins that have been flash-frozen in vitreous ice (without
crystals) to obtain high-resolution images of their natural shape and form.

What emerged was a large, mushroom-shaped structure—one of the largest bacterial secretion
systems ever described. The discovery opens the door for future studies to determine how the pieces
of the “injector” fit together and function.

Since type IV secretion systems are produced by many bacterial species, including those that are not
pathogenic to humans, “the results of this study will eventually help us understand how these
systems carry out a wide range of di!erent functions,” Cover said.

VUMC has the article

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