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When a population of bacteria is large enough, individual bacteria can communicate with each other to coordinate attacks on larger species while saving resources within its own population — a process called quorum sensing. This process can lead to issues associated with bacterial growth such as infection.

At the Blackwell Lab at the University of Wisconsin’s Department of Chemistry, UW senior and undergraduate researcher Stella Ma is exploring new means of treatment for approaching bacterial issues in a more efficient manner.

“Communication is involved in the attack behaviors of a lot of pathogenic bacteria,” Ma said. “We’re thinking if you inhibit quorum sensing, the bacteria won’t be as dangerous to a person.”

Bacteria use signaling molecules that are short peptides of amino acids for quorum sensing, Ma explained. The Blackwell Lab is studying aspects of the bonding and activating properties of these molecules so they can modify them to inhibit quorum sensing.

Inhibiting quorum sensing in bacteria is drawing a lot of attention in terms of disease control, Principal Investigator and UW Professor Helen Blackwell said in an email to The Badger Herald. This involves “retailoring” signal molecules to make artificial signals which confuse the bacteria.

It is important because quorum sensing plays a role in human infections that have a massive toll worldwide,” Blackwell said. “It’s also important as we simply don’t understand a lot about how quorum sensing works, so we are trying to work that out in my lab.”

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Ma is examining a foodborne pathogen called Listeria monocytogenes. The FDA had numerous food recalls related to listeria and contaminated food can be particularly dangerous because it can result in miscarriages during pregnancy.

When listeria do quorum sensing, they create a protein called chitinase to interfere with the immune system, Ma said, which breaks down the molecule chitin. In observing the role of quorum sensing inhibitors, Ma was probing listeria’s ability to break down chitin.

“I think there’s a lot of potential for quorum sensing inhibitors in medicine. They work really well in mice and they work really well for preventing bacteria build up on surfaces,” Ma said.

Ma started research in the Blackwell Lab her freshman year. She began with working on an X-ray crystallography project. Quickly, Ma found herself fascinated with quorum sensing and has been a part of the lab since.

Graduate student Korbin West is Ma’s mentor in the Blackwell Lab. They have been working together since Ma started research in the lab during her freshman year and together they developed a quorum sensing inhibitor for listeria.

“I found the research super interesting and the lab is super nice. They’re really welcoming and they’re really supportive of undergraduates,” Ma said.

Ma was required to complete a research project for her Chem 116 class in her freshman year and she said that’s how she started the X-ray crystallography project. When the project was over, she approached West about continuing research with the group.

Ma was interested in the research at the Blackwell Lab from the start, she said, as she was always curious about the chemical side of the biological processes she learned about. This lab gave her an opportunity to explore the intersection of these topics.

She brings a strong interest in human health, medicine and immunology, which balances our more chemical approach,” Blackwell said.

Before the pandemic, Ma was collaborating with an immunology research lab with zebrafish. She would infect zebrafish with listeria and observed how the infection cleared in the presence of quorum sensing inhibitors.

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Ma was able to observe only a few successful experiments before the COVID-19 pandemic hit, she said. The results were preliminary, but it seemed fewer immune cells were present at the site of the infection when quorum sensing was inhibited.

Bacteria can build up and cause issues in a lot of settings, Ma said, particularly in hospital settings, such as buildup in catheters. Many researchers are trying to use communication inhibitors to prevent bacterial growth on important surfaces.

“The main goal of the lab is to find non-antibiotic ways to treat bacterial infections and also to make materials to help stop bacteria from growing on surfaces,” Ma said.

Quorum sensing in listeria hasn’t been very well studied and West said building this foundational knowledge of the behaviors that can be affected by inhibiting communication could be applied to different scenarios.

One such behavior of listeria that could be prevented by quorum sensing inhibitors is the formation of biofilms, which are sticky substances that attach to surfaces and are difficult to remove, West said.

Studying listeria has a lot of applications as biofilms show up in the food industry quite a lot and infection outbreaks occur about a dozen times a year, West said. According to West, listeria has a fatality rate of about 30%. Inhibiting quorum sensing in listeria could help with these issues.

“We’re not making drugs in the Blackwell Lab, but we’re providing tools to study these organisms and maybe one day these will lead to effective drugs,” West said.

Inhibiting quorum sensing provides a different path to treating bacteria than antibiotics, which could be vulnerable to antibiotic resistance because some bacteria will inevitably survive antibiotics, Ma said. Blocking quorum sensing can prevent group attacks from bacteria without having to selectively kill bacteria cells.

Blackwell said Ma has been a valuable asset to the team from early on. Ma has assisted in many projects and after her graduation this spring, she will be conducting research on COVID-19 and HIV immunology at the National Institute of Health.

“She’s really hardworking and she thinks a lot about the things she does,” West said. “She does good science. That’s everything a mentor would want.”