Study in progress could point toward different approach to UTI treatment

By investigating how bacteria can survive and thrive in the bladder, a team of undergraduate researchers at Binghamton University hopes to help millions of women worldwide suffering from recurrent urinary tract infections (RUTIs).

"Anytime I talk to other women, either different professors or just students here, and I tell them that I'm researching recurrent urinary tract infections, they're like, 'Oh my God, please find out more information,'" said Katherine Peters, a senior majoring in biomedical engineering and one of the research assistants in the Mahler Lab. "RUTIs are different than UTIs, and they just come back, and there really isn't much known about them that helps prevent it."

Peters, who was recruited into the Mahler Lab in 2023 through the Research Experience for Undergraduates (REU) Biofilm program, has worked closely with Sydney Nierdstat and Rachel Proper since 2024 to study the development of RUTIs. Led by Gretchen Mahler, professor of biomedical engineering, the lab focuses on organ-on-a-chip technology and creating physiologically realistic models to study cellular responses to disease, drugs and chemicals.

"Katherine, Rachel and Sydney have all been fantastic to work with and are developing into great researchers," Mahler said. "We have a team working on this project that includes undergraduate students, graduate students, a postdoc, multiple faculty members and an MD. All of these women have become well-integrated into the team and work well with everyone else."

Mahler also collaborates with Claudia Marques, an associate professor of biology who specializes in multispecies biofilms and persister cells, and Dr. Jennifer Hill, a local urologist and urogynecologist who collected samples from her RUTI patients.

"We hypothesized that the multiple [bacterial and fungal] species present, potential formation of biofilms and build up of fibrin could all be contributing to difficulties in curing these patients' UTIs," Mahler said. "The research project at BU started to try to develop a cell culture model of RUTI to test this hypothesis."

According to their preliminary research, 82% of patients with RUTIs have a gene mutation that leads to higher levels of fibrin—a protein that can build up to create the ideal environment for harmful bacteria growth and antibiotic resistance.

Using in-vitro fibrin gel models that replicate conditions of the intestinal system, the team compares cell growth and bacterial behavior in fibrin versus non-fibrin environments.

Nierdstat, a junior majoring in biomedical engineering, and Proper, a senior majoring in biochemistry, take the lead in cultivating cells and strains of E. coli and E. faecalis—the two most common culprits responsible for RUTIs. They then track cell viability under a microscope with fluorescence, observing irregular clumping and increased counts of dead cells due to the presence of fibrin.

"We've also found that bacteria grow more in the fibrin, which is what was expected," Peters said. "But of course, we had to do the research to find that out. That was one of the main findings, that the fibrin does create a biofilm where the bacteria can resist the antibiotic more."

In addition to studying how the two strains interact under fibrin, the lab also tested three different types of treatment against RUTIs. They found that the commonly prescribed antibiotic ciprofloxacin only works against E. coli and had virtually no effect on E. faecalis. Without identifying the right kind of bacteria responsible for the infection, health care providers may be unknowingly prescribing ineffective treatment.

"In the hospital setting, if someone is diagnosed with an RUTI and the people diagnosing them don't know what bacteria they're dealing with, they might prescribe the wrong medication," said Proper, who was drawn to the project because of its applications to antibiotic resistance. "It necessarily wouldn't be harmful, but it wouldn't benefit them. I feel like observing the differences between different bacteria or different treatments in general will help get an overall impression of what they're working with."

While the team is still in the early stages of its research and the students understand that they might not be the ones to find a cure, they're enthusiastic about the possibility of helping patients. Collecting this data may build the foundation for future breakthroughs in diagnosis and treatment.

"There's not a lot of data on women's health, specifically recurrent UTIs," Nierdstat said. "So I like that I'm able to contribute my part in trying to expand the data that we can find on things, and maybe get better treatment."

Binghamton University