Hormel Institute Researchers Receive $19K Venn Foundation Grant, Publish Findings That Could Lead to New Class of Antimicrobial Treatments

Jarrod French, PhD, Associate Professor at The Hormel Institute, University of Minnesota in Austin, is the recipient of a two-year, $19,000 grant from the Venn Foundation that will support a project aimed at developing a new class of broadly applicable, immune-enhancing antimicrobial treatments. In progressing with this project, Dr. French and lab researcher Dr. Faisal Aziz have also recently published a paper in Journal of Medicinal Chemistry, which identifies and characterizes a set of compounds that block the function of a protein that suppresses the immune system — a discovery that could improve treatments for infectious diseases and save countless lives.

Over five million people worldwide die each year from infectious diseases with an estimated global economic impact of over $8 trillion (nearly a tenth of the entire global economy). Making matters worse, bacteria and other microbes are becoming increasingly resistant to anti-microbial drugs. Many of these infections are hospital-acquired and often affect people whose immune systems are weakened.

However, it’s possible that new research may help to reduce these numbers. In collaboration with Dr. Nick Carpino at Stony Brook University, the French lab studies a protein known as STS that serves as an immune response repressor, essentially “turning off” immune system responses when activated, similar to the way brakes on a car help it stop.

The researchers found that when STS is inactivated — i.e., when the foot is taken off the brake pedal — the immune system has a much better response to infection. This includes faster pathogen clearance, faster recovery times, and ultimately, higher survival rates.

Now, the French lab is working to develop small molecule therapeutics (drugs) that can
inactivate this protein in order to fight infection.

“We recently identified some small molecules that can inhibit the protein target of interest,” said Dr. French. “This grant will allow us to scale up the production of these molecules for additional studies and enable us to create variants of these compounds that have more favorable properties.

“If successful, this work is expected to lead to the development of a new class of immune-enhancing antimicrobial treatment. Because this approach enhances the immune system and does not specifically target the microbe, it has the potential to be effective against a wide range of bacterial and fungal pathogens.”

If you’re curious to learn more about the project, you’re in luck. The French lab recently published a paper entitled “Rebamipide and Derivatives are Potent, Selective Inhibitors of Histidine Phosphatase Activity of the Suppressor of T Cell Receptor Signaling Proteins” in Journal of Medicinal Chemistry. Drs. French and Aziz are listed as authors.

In this study, researchers used high-throughput screening, a method commonly used in drug discovery for rapid testing of a large amount of samples, and were able to identify compounds (called hits) that inhibit STS. X-ray crystallography allowed them an up-close look at how the STS protein interacted with the compounds.

As you might be able to deduce from the title, a particular compound known as rebamipide was found to effectively inhibit STS activity. Rebamipide is already used to treat ulcers and gastritis in several Asian countries.

“Rebamipide is a drug with a good safety profile and many years of history of safe use,” said Dr.
French. “This discovery could help to accelerate the development of safe variants that could be
used as antimicrobial treatments.

“Infectious disease kills millions each year, and resistance to current antimicrobial treatments is increasing. New methods to treat infectious disease are desperately needed. Successful completion of this project could lead to new antimicrobial therapies that save millions of lives.”