Mueller Brown Studies How Pneumococcal Bacteria Communicate

Karina Mueller Brown's work sometimes follows her home. The recent Ph.D. graduate in biological sciences studies Streptococcus pneumoniae, a pathogen that lives in the nasal passages of nearly half of all children, including — most likely — Mueller Brown's young daughter.

"There are occasions when I'm helping my daughter wipe her runny nose and wondering what the bacteria are up to in there. That's how geeky and nerdy I am," she jokes.

Mueller Brown is the 2023 recipient of the Bhakta and Sushama Rath Graduate Award, which supports a Ph.D. student in a STEM field whose research benefits U.S. industry or societal needs.

S. pneumoniae, commonly called pneumococcus, causes more than a million annual deaths worldwide, especially in young children and the elderly. The World Health Organization identified pneumococcus as a priority pathogen, and the bacterium is on the Centers for Disease Control and Prevention's list of serious threats.
 

While it can present as a major pathogen, pneumococcus doesn't always cause disease. A community of pneumococcus can colonize the nose and throat without causing any further symptoms, but if these bacteria migrate to other tissues, they can cause dangerous illnesses. Mueller Brown wants to know why and how they turn pathogenic.

"All the little details of how they get you sick fascinate me, but my work focuses on how the bacteria communicate to their neighbors that it's time to make the switch," said Mueller Brown, who works in the lab of N. Luisa Hiller, an associate professor of biological sciences.

Pneumococcus exists in complex bacterial communities, where each individual bacterium produces and receives signals to sense the host environment and communicate with its neighbors.

The bacteria use many different systems for communication, each of which involve different signaling molecules. Each system has a distinct function related to staying asymptomatic or turning pathogenic. Scientists have characterized each system, and now Mueller Brown has uncovered a link indicating that the systems likely have to coordinate in a certain manner to cause disease.

"The interesting part is that this coordination is only detected when it has a host. You do not see it when you grow the bacteria in a culture, but if you grow them with a cell culture line of lung cells (because it is a pathogen of the respiratory tract), that's when we can actually see this pathway being turned on and off," she explained. "The host is actually what triggers this mechanism."

Mueller Brown presented the work at EuroPneumo 2022 in Liverpool, England, at a Gordon Conference in Maine, and at the 2023 Mid-Atlantic Microbial Pathogenesis Meeting in Virginia.

"Karina's most recent data demonstrated that a single transporter links two families of cell-cell communication peptides and may have important implications on strategies to develop anti-pneumococcal drugs," said Hiller, in whose lab Mueller Brown will continue on as a postdoctoral research fellow.

In another recent project, Mueller Brown characterized a complex communication system that utilizes 'competition molecules' to help pneumococcus compete with other microbes in the nose for limited nutrients and resources. Because the bacteria can have a dozen or so of these putative bacteriocins, analyzing the system was a complex task, which is why Mueller Brown teamed up with Sien Tam, a master's degree student in the Department of Computational Biology. Together they took a computational approach.

"This locus is one of the most diverse systems we have characterized in pneumococcus. Because it's so diverse, it was very hard to design experiments," Mueller Brown said. "But now that we have the baseline of understanding all the different components, we're going to move forward and try to do some exciting experiments."

Mueller Brown's Ph.D, which she earned in June 2023, focused on bacteria and pathogenesis, but now she has her sights set on studying the host.

"I've acquired some sort of expertise on what pathogenic bacteria does. But I want to understand now what happens on the other side of things. I'm excited for that next stage," she said.

During her time at Carnegie Mellon, she said she has enjoyed working with Hiller, her fellow graduate students and undergraduates, and her many collaborators.

"I had such wonderful collaborators for all of my projects. I am incredibly grateful. My projects couldn't have been as awesome as they are if I hadn't had all these amazing people work with me and collaborate," she said.

She currently is applying to her next postdoctoral position, but beyond that, Mueller Brown is still undecided whether she will stay in academia or try her hand in industry to delve into therapeutics. 

"My interest is to find a cure for diseases. It always has been," she said. "Becoming a mother in the midst of the COVID-19 pandemic, I'm now more encouraged and motivated than ever."