Scientists Identify Compounds That Render Listeria Nonpathogenic

A new study has identified compounds that can reduce the virulence of the pathogenic bacterium Listeria monocytogenes.

James A. D. Good, PhD, from Umeå University in Sweden, and colleagues published the results of their study in the journal Cell Chemical Biology.

Listeria monocytogenes is ubiquitous in nature and can be transmitted to humans and animals via the food chain. Once ingested, it can cause gastroenteritis. “Its ability to grow at low temperatures, in high-salt and low-oxygen conditions, makes L. monocytogenes one of the most problematic foodborne pathogens,” the authors say.

The bacterium is most commonly found in raw foods, including unpasteurized dairy products and raw meat. Processed foods, such as soft cheeses and cold cuts at the deli counter, can also become contaminated after processing. And unlike many other bacteria, Listeria can grow in the cold temperature of the refrigerator.

Whereas immunocompetent individuals typically clear the infection within a couple of weeks, immunocompromised individuals are at increased risk of developing listeriosis, a commonly fatal infection of the bloodstream and central nervous system. In pregnant women, the bacterium can also cross the placenta, infect the fetus, and may result in spontaneous abortion.

“In light of increasing antibiotic resistance, novel therapies are required to potentiate or succeed our current selection of therapeutic options.” the authors emphasize.

In particular, interference with bacterial virulence represents a compelling therapeutic approach because it is considered to result in less selective pressure for the development of bacterial resistance than traditional strategies—which aim to kill bacteria or prevent their growth—result in. As a consequence, inhibitors of virulence in pathogenic bacteria are now emerging.

With this in mind, Dr. Good and colleagues conducted a study to identify chemical compounds that can target the virulence of L. monocytogenes rather than its viability.

Using cell culture techniques, the team infected human cells with L. monocytogenes and tested the ability of many ring-fused 2-pyridones to inhibit bacterial virulence. These compounds are pilicides that inhibit pilus formation in L. monocytogenes.

They found that some of the ring-fused 2-pyridones not only prevented the bacterium from infecting the cells, but also reduced the expression of its key virulence genes by binding to PrfA—an important virulence regulator that controls the pathogenic mechanisms of Listeria.

On the basis of the results of this study, the authors emphasize that these inhibitors, “are a new set of tool compounds for improving our understanding of L. monocytogenes virulence.”

“Translating this research into a clinical application requires more effective inhibitors and in vivo proof-of-concept, but these findings represent the first steps in this process of identifying new therapeutic opportunities to treat infectious diseases,” they conclude.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.