By JAKE MILLER Research

6 min read

Fluorescence microscopy image of cultured cells showing green listeria trailing red comet tails of actin filaments. The background is black, making the brightly colored bacteria and cellular structures stand out vividly.
Listeria (green) moving within the cytoplasm of lab-cultured human cells. The bacteria are propelled by comet-like tails formed from host cell actin (red). Using actin-based motility, listeria can propel itself out of the host cell to directly infect neighboring cells and spread across internal barriers such as the blood-brain barrier and fetal-placenta barrier. Image: Higgins Lab

Six people have died and 25 have been hospitalized across 18 states from illness caused by food contaminated with Listeria monocytogenes since an outbreak linked to precooked meals was first reported by the U.S. Centers for Disease Control and Prevention in July 2025. Listeriosis is the third-leading cause of death from food poisoning in this country, and it’s particularly dangerous for people who are over 65, pregnant, or immune compromised.

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Darren Higgins, professor of microbiology in the Blavatnik Institute at Harvard Medical School, has been studying listeria and other so-called intracellular bacteria for decades. Understanding how these bacteria enter, reproduce, and thrive inside host cells — as opposed to extracellular bacteria, which reproduce outside cells in places like blood and mucus — is key to finding better ways to prevent and treat the illnesses they cause and to deepening our understanding of human health, Higgins says.

Higgins spoke with Harvard Medicine News about the unusual biology that makes listeria and similar pathogens so deadly and how he’s endeavoring to use their cellular, genetic, and molecular machinery to devise tools to fight infection.

Harvard Medicine News: What makes intracellular bacteria like listeria different from other bacteria that cause food poisoning?

Darren Higgins: Listeria can use human cells as places to hide from the immune system and as a way to travel to sites within the body that most bacteria can’t reach, like across the membrane that protects the brain and across the placenta to infect a developing fetus.

For people with immune systems that are compromised due to age, pregnancy, or some other reason, listeria has the highest case fatality rate of any food-borne pathogen — we’ve seen as high as 20 or 30 percent in recent outbreaks.

There are currently no targeted treatments for listeria infection. If a pregnant person gets sick, you’re looking at a month or more in the hospital with high-dose intravenous antibiotics and still there is a high risk of fetal mortality, premature labor, or stillbirth due to the infection.

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HMNews: What is the value of basic scientific research in trying to solve the problem? What are the most important questions you’re hoping to answer?

Higgins: We’re using what we learn about the basic biology of these bacteria to try to find ways to prevent and treat these infections.

Some questions are: How does listeria persist in the environment? How does it get inside cells and thrive once it’s in there? How does it travel between cells to spread the infection?

And specifically, how does it cross the blood-brain barrier and the placenta to infect the central nervous system or a developing fetus?

The more we know about these mechanisms, the more chances we will have to intervene.

HMNews: Why is it important to understand how listeria can persist in the environment?

Higgins: These bacteria are commonly found in the soil. One of the worst outbreaks since the CDC started tracking them in the 1970s was from cantaloupe. The melons were sold with soil on the outer rind that had a potent strain of listeria in it. When people cut into the melon without washing it, the bacteria spread to the part of the fruit that they ate.

In many cases, thoroughly washing or cooking your food is enough to prevent infection from listeria.

But listeria’s surprising staying power in different environments can make that challenging. For example, it can grow at refrigeration temperatures, and it can form a persistent biofilm — a kind of slime that sticks tenaciously to non-biological surfaces, like a knife that’s used to cut a lot of different cantaloupes or a stainless-steel meat slicer. Once it’s there, it can contaminate all the food that touches it. If you buy food that is contaminated, the bacteria can continue to grow in your fridge. Which means a single bacterium on a piece of meat in a sandwich or a heat-and-serve burrito can grow into a dangerous number in a relatively short period of time. That’s why it’s so important to be careful with expiration dates for prepared foods.

HMNews: Do existing sterilizing products work to prevent this type of contamination?

Higgins: Bleach kills listeria very well, but it also can kill people. UV irradiation works without cooking the food, but it causes breakdown at the cellular level, which changes the taste of food. You can also use high temperature to cook the food, but people don’t want boiled cantaloupe. Cooking kind of ruins the whole point of cold cuts or fresh fruit and vegetables. The goal is to create a way to prevent contamination that’s not toxic and that lets people enjoy the food they love.

HMNews: What have you found that could help?

Higgins: We figured out that listeria relies on a certain kind of appendage to grasp surfaces when it forms a biofilm. We’ve found clues we can use to block that process chemically. We’re hoping we can make a product that prevents the formation of these biofilms and makes it easier to wash away the bacterial contamination.

HMNews: How does listeria get into the body and then spread to cause infections that can be life threatening?

Higgins: It enters through the gut. If it gets into the blood, it detects signals that tell it to start producing factors to allow entry and growth inside of human cells. We have a new project to understand how this signaling works in hopes that we can interrupt it and slow down the spread of infection. One of the ways the bacteria kills a person is by causing a systemic blood infection known as sepsis. It also kills by infecting the central nervous system, including the brain. Bacteria carried by the blood and the lymph fluids can rapidly spread to different tissues and organs.

Darren Higgins on why he loves science.

Sometimes listeria infects white blood cells and uses them as a Trojan horse to spread throughout the body. Some pathogens do this by growing inside a cell and then bursting their host cell to get out and start all over again. Listeria is able to stretch the membrane of the cell it is living in to form long protrusions that make tunnels into nearby cells.

HMNews: How would you go about stopping the bacteria from spreading from cell to cell

Higgins: The key is to understand the whole fascinating process they use to pull this off. To start with, listeria makes a protein that summons actin, one of the building blocks that our cells use to build all kind of structures. The actin forms a kind of propulsion system that sends the listeria shooting around the inside of the cell. The actin trails behind the moving bacteria, like the tail of a comet.

When the bacteria hit the cell membrane, instead of bouncing off they push the membrane out and make these protrusions. Instead of springing back into shape, the protrusions continue to get longer and longer. Eventually the protrusion pushes its way into the interior of another cell, and the bacteria can infect the neighboring cell without ever travelling outside.

We have a new study that is not yet published that describes how these protrusions form without rupturing the cells. This discovery could help us develop tools that interfere with the bacteria’s ability to spread and cause severe infections. The bacteria will then lose much of their ability to cross the blood-brain barrier or the maternal-fetal barrier.

HMNews: What have you found about what drives the bacteria to the brain?

Higgins: In 2017 my lab started studying bacterial strains collected from patients from some of the deadliest listeria outbreaks we’ve had in the United States to understand more about how these severe infections develop. It turns out the outbreak listeria strains are quite different from the more common laboratory strains. One key thing about the outbreak strains is that they get to the brain more successfully than the standard strains.

Decades ago, microbiologists figured out that listeria make dozens of different proteins that can bind to multiple receptors on human cells, but until recently scientists couldn’t pin down any link from the proteins in the lab strains to the receptors in the brain. We discovered that the deadlier strains make proteins that work well with a specific receptor prevalent on brain cells and on the cells that form the lining that protects the brain from infection.

We knocked out the bacterial gene that makes that protein and saw a significant decrease in the deadlier listeria strains’ ability to go to the brain.

We’re hoping these clues will point us toward a therapy that could prevent listeria from infecting the brain and conceivably could be a useful tool against all kinds of brain infections.

HMNews: So this work is not just about listeria.

Higgins: That’s one of the most exciting aspects of this research. Our work has the potential to directly contribute to preventing and treating these deadly listeria infections, but we’re also making discoveries about more fundamental biology that can help us understand bigger questions.

Our work has provided insights into how other intracellular bacteria — like those that cause shigella, chlamydia, and tuberculosis infections — function, and other labs have applied our work to non-bacterial pathogens such as the malaria parasite, herpes simplex virus, and hepatitis C virus. We’re also learning new things about how the immune system changes as people age, which will be helpful across a number of illnesses and conditions.

This is why I love science so much. I’m working to make it possible for people to have healthier lives, and I’m making all these new discoveries about the fundamental secrets of life.

This interview was edited for length and clarity.

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