Wash Your Hands: USU Biochemist Studies the Molecular Mechanisms of Food-Borne Illness

As Americans approach the Thanksgiving holiday, thoughts of turkey, mashed potatoes and that all-time favorite pumpkin pie come to mind. Most revelers will gobble delectable delights without incident (other than a so-called “food coma”), while enjoying the holiday meal and a football game. An unlucky few may suffer worse effects that will, hopefully, subside with time, multiple bathroom visits and some tender loving care.

All jesting aside, food and water-borne illnesses are no laughing matter. Utah State University biochemist Sam Barker reports diarrheal diseases are a leading cause of death worldwide, hitting children, the elderly and those with compromised immune systems particularly hard.

The Soda Springs, Idaho native is a recent doctoral graduate in USU’s Department of Chemistry and Biochemistry. In the lab of faculty mentor Nick Dickenson, Barker, who earned a bachelor’s degree from Utah State in 2018, studies a gram-negative genus of bacteria, known as Shigella. The bacterium causes a nasty gut bug in humans called shigellosis.

“In developed countries, shigellosis is not generally fatal,” he says. “But the diarrhea-causing illness, which is spread along the fecal-oral route from person to person, is responsible for more than 100 million cases worldwide and nearly 600,000 deaths annually.”

In poverty-stricken communities short on water and adequate sanitation, shigellosis outbreaks can be hard-hitting. While most people recover on their own without antibiotics, certain strains of the bacteria cause more serious illness and are becoming increasingly antibiotic-resistant. And that rising resistance has pushed Shigella into the spotlight.

“The World Health Organization has promoted Shigella from a medium to a Priority-2-High pathogen this year due to its rising resistance and the substantial burden it places on communities,” Barker says. “The race is on to develop new antibiotics to combat infection as well as a vaccine to prevent infection.”

Both of those aims, he says, require a better understanding of the structure and function of the bacterium. The rod-shaped Shigella flexneri wields a needle-like Type Three secretion system (T3SS) apparatus, with invasion plasmid antigen D, known as “IpaD” at its tip. It uses this apparatus to inject protein effectors, carried into the human gut in contaminated food, into the small intestine’s epithelial cells.

“Along this route, the bacteria are exposed to the bile acid deoxycholate or ‘DOC,’ which functions as an environmental signal allowing shigella to begin their invasion of M cells — also known as microfold cells,” Barker says. “Immune cells called macrophages resist the bacteria, which fight back with their sword-like T3SS apparatuses and the battle is on. If the Shigella bacteria can successfully pierce and invade cells, a disease state results.”

Using advanced crystallography and microscopy techniques, Barker further characterized DOC effects on T3SS needle tip construction.

“What I found was the bacteria’s exposure to the bile acid led to maturation of the formidable needle-tip with the formation of a rare secondary protein structure called a ‘pi helix,’” he says. “This structure prevents the bacterium from releasing its protein too soon and missing the target. The pi helix, we discovered, is the critical element in the sensor, signal and response pathway allowing the bacterium to successfully infect a healthy cell.”

This knowledge, Barker says, could aid development of new vaccines and treatment strategies to combat shigella.

“Preventing infection or stopping it in its tracks could have a big impact in curbing dangerous disease outbreaks — especially in areas where water supplies are compromised by natural disaster or war,” he says.

In the meantime, if you have access to clean water, be grateful, Barker says.

“Remember to wash your hands with soap and water before preparing food or eating food,” he says. “It’s a privilege and a sound, easy precaution against illness.”