19 Feb 2016

Gut reaction: understanding the cause of ulcers and stomach cancers, and how to stop them

SASKATOON (Friday, February 19, 2016) – Ulcers. They are not only painful and difficult to deal with, but the same bacteria that cause ulcers can lead to stomach cancer and other diseases of the human intestinal tract. But, there is hope.

Scientists from the University of British Columbia, the University of Washington, and the Fred Hutchinson Cancer Research Centre in Seattle, have made an important discovery into understanding, and possibly preventing, nasty gut bacteria from making us sick.

There are two bacteria that UBC Professor Martin Tanner is especially interested in: Helicobacter pylori – the causal agent of ulcers and gastric cancer – and Campylobacter jejuni – one of the primary causes of human food poisoning that can also result in the development of Guillian-Barré syndrome.

H. pylori are helical-shaped bacteria that are human pathogens and live in the gut,” says Tanner. “They must escape the acidic environment of the stomach and colonize in the mucous membranes of the stomach lining. Their ability to do so is aided by their corkscrew shape that helps them to burrow into this viscous environment.  Similarly, C. jejuni require a helical shape to colonize the intestine.”

Tanner and his team used the Canadian Light Source to discover an inhibitor that targets an enzyme called Csd4 protease, which controls the helical cell shape in the human pathogens H. pylori and C. jejuni. By treating the pathogens with an inhibitor, they were able to induce cell straightening, preventing the formation of the corkscrew shape and the ability to burrow into the lining of the gut.

“This work suggests that the Csd4 protease is a reasonable target for further antibacterial design,” says Tanner. “We’ve shown that even compounds that are typically not good drugs, as they do not enter cells readily, can reach the cell wall where the target enzyme is located.”

Tanner thinks that a molecule designed to bind with the Csd4 protease would alter the bacteria's shape, essentially turning the corkscrew into a straight rod, and reduce its pathogenicity by limiting its ability to burrow into the lining of the gut. 

“This work provides further evidence that cell shape-determining enzymes are reasonable targets for the future development of antibacterials. It also provides us with a tool that could be helpful in understanding the fundamental processes that control cell shape during bacterial growth.”

Scientifically, the research shows incredible promise for the maintenance of intestinal health, by understanding the helical shape of the bacteria and how it is directly related to their ability to colonize.

From a purely aesthetic standpoint, Tanner thinks “it is cool to be able to design a compound that when sprinkled on helical bacteria, makes them straighten out.” 

 

Contact:

Mark Ferguson 
Canadian Light Source
306-657-3739

figure: the corkscrew shape of the bacteria allows it to burrow into the lining of cells and cause ulcers and other diseases. The enzyme inhibitor can cause the bacteria to straighten out. Courtesy of Martin Tanner, UBC.
Cite: Liu Y, Frirdich E, Taylor JA, Chan AC, Blair KM, Vermeulen J, Ha R, Murphy ME, Salama NR, Gaynor EC, Tanner ME. A Bacterial Cell Shape-Determining Inhibitor. ACS Chemical Biology. 2016 Jan 15. DOI: 10.1021/acschembio.5b01039  

 

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