Tu-Anh Huynh is uncovering how a single molecule can help fight a common pathogen — and its resistance to antibiotics.
Tu-Anh Huynh spends much of her time tracking tricksters that alter their shape and function to survive in extreme conditions. In other words, she studies bacteria.
Unique among such change artists, the pathogen called Listeria monocytogenes (listeria) has long fascinated Huynh with its ability to grow in cold refrigerators and garden soil. It thrives under preservation and harsh storage conditions, where most other bacteria don’t survive, and infects more than 40 animal species, including humans. Listeria can easily contaminate many types of foods, such as poultry, hot dogs, lunch meat, melons, unpasteurized cheeses, and coleslaw. And although listeria infection (listeriosis) occurs through eating contaminated foods, it can go on to cause severe infections in susceptible people, also called the YOPI group (young, old, pregnant, immunocompromised). Each year, an estimated 1,600 people contract listeriosis, and about 260 of them die, according to the Centers for Disease Control. Huynh wants to change those numbers.
As an assistant professor of food science and microbiology, Huynh focuses her research on bacterial signaling, or how bacteria — such as listeria — identify their surrounding environment, locate nutrients, avoid hazards, and sometimes communicate with other bacteria. In particular, she’s looking at how a messenger molecule called cyclic-di-AMP (c-di-AMP) can govern this process.
Huynh’s research group has already found that when bacteria can’t maintain proper control of c-di-AMP levels, they become very sensitive to many antibiotics. By learning more about how c-di-AMP regulates antibiotic resistance, Huynh wants to disrupt its balance to combat bacterial infections in humans and animals.
What drives you to study listeria?
Listeria is an important human and animal pathogen, so we want to learn how it adapts and responds. We want to do that at both the molecular level and the population level — looking at listeria as a group of organisms.
Because this pathogen is so adaptive and can survive in so many locations, it’s notorious for being introduced within butchered meat or other products in food processing plants and can persist for decades.
It’s also good at growing in the cold — in refrigerators or in winter, under grass, where cattle will graze on it after the spring thaw. That often causes listeria outbreaks among cattle in the spring, which can affect farmers, the food supply, and processing plants.
And we want to understand why c-di-AMP is essential to listeria’s antibiotic resistance. If listeria cannot regulate c-di-AMP, the bacteria fall victim to antibiotics that target the cell wall; that’s certainly what we want to happen. In our [November 2020] Journal of Bacteriology paper, we learned if you disrupt the c-di-AMP balance in listeria, the bacteria become more susceptible to antibiotics.
How did you get interested in bacteria signal messengers?
As an undergrad, I worked in a lab studying microbial ecology in food fermentation. I had a project looking at how biochemical activities by different microbes contribute to cocoa bean fermentation — how they interact with one another to produce yeast, ethanol, and heat. The high temperature in those products kills the beans and creates the flavoring of chocolate. I became interested in the tiny processes within biology and took it from there. In graduate work, I studied bacterial signaling mechanisms, exploring how bacteria identify environmental signals to adjust their growth and reprogram themselves.
Toward the end of my doctoral work, c-di-AMP was discovered. At the time, it was a completely novel second messenger molecule synthesized by bacteria. Excited by this, I decided to pursue postdoctoral training on its signaling mechanisms.
What excites you about your work?
I’m excited that, in terms of antibiotic resistance, we’re exploring a pathway — controlled by c-di-AMP — that isn’t well studied yet. Trying to understand how listeria acquires antibiotic resistance and passes it around to other bacteria among agricultural animals is also a unique approach.
The work we published in the Journal of Dairy Science provided valuable information about the prevalence of antibiotic resistance in listeria among a small number of animals in Wisconsin, which is essential information in managing the spread of antibiotic resistance.
Understanding how c-di-AMP works can lead to the development of new antibiotics. If we can block that messenger molecule, that might be a good way to target antibiotics to make them more effective.
How did being at CALS help with this work?
In my program, I enjoy exploring research directions I wouldn’t have thought of before arriving in Madison. For instance, I began studying listeria in the feces of dairy cattle because of the vibrant dairy research community here in the Dairy State.
For cattle work, I coordinate with the director of the Wisconsin Veterinary Diagnostic Laboratory, Keith Poulsen BS’00. Along with directing the lab, he is a large animal vet who connected me to dairy farms and advised us on animal physiology and reproductive health. He helped us select the 20 animals we worked with in our study.
To follow up on our studies, I’m working with the rest of my lab members to understand what underlies antibiotic resistance among Listeria monocytogenes isolates from dairy cows. We’re also exploring the molecular pathways that c-di-AMP regulates within the bacterial cell so that we can manipulate them for therapeutic and genetic engineering applications.
Huynh’s c-di-AMP Findings and Implications
In November 2020, Huynh coauthored a study in the Journal of Bacteriology finding that, much like a shortage of c-di-AMP can cause problems for bacteria, too much of the signal messenger in certain spots could make it vulnerable to the antimicrobial agents used in many antibiotics.
In the April 2021 issue of the Journal of Dairy Science, Huynh and a research team reported finding resistance to the antibiotic ampicillin (and, to some extent, gentami-cin) in listeria that was sampled from the feces of a herd of lactating dairy cattle in Wisconsin. They detected a greater abundance of certain strains of listeria in cows that were shedding the pathogen and suggested that targeting the strains present within a particular ecological niche may be a more effective control strategy. This is an important finding because listeria in cattle feces can spread to the herd — and within the human food supply.
This article was posted in Food Systems, Health and Wellness, Living Science, Spring 2022 and tagged antibiotic resistance, Antibiotics, bacteria signal messengers, c-di-AMP, cyclic-di-AMP, dairy cattle, Food science, listeria, Microbiology, Tu-Anh Huynh.