Fighting to prevent infections

Notre Dame researchers have created a novel catheter adaptation that prevents infections before they begin.

Before entering the patient’s room, Dr. Barbara Trautner dons a plastic gown, mask, and gloves. The patient is one of many with Candida auris, a fungus known for being particularly resistant to anti-microbials and is frequently found in hospital settings. To try to reduce spread, Trautner will dispose of all her gear when she is done speaking to the patient. The nurses who rotate in and out of the room all day long will do the same, over and over again. Heaps of discarded gear seem wasteful, but Trautner, the Gerald and Judith Medoff Professor of Infectious Diseases and the co-chief of infectious diseases at Washington University’s Department of Medicine, says mitigating the spread of the fungus is critical.

Candida auris is one of many microbes found in hospital settings and can cause seemingly benign infections like urinary tract infections (UTI).

Diagram of a human body showing skeletal, nervous, and vascular systems in different colors.

How catheters can cause serious infections
For patients with catheters, a small tube used to drain the bladder for everything from C-sections to spinal cord injuries, exposure to pathogens can be particularly risky.
As Trautner said, “When you put in a urinary catheter, you violate the bladder's natural defenses of voiding out urine regularly and you basically establish a superhighway for bacteria.”
Under normal conditions, bacteria entering the bladder will get flushed out…
…but the tiniest kink or blockage in the tubing can lead to build up and infection, Trautner explained.
Each year in the United States, there are more than one million catheter-associated urinary tract infections (CAUTI). While a UTI may seem innocuous, it can be anything but. Left untreated, these infections can turn into blood infections, prostatitis, cystitis, endocarditis, vertebral osteomyelitis, septic arthritis, meningitis, and even bladder cancer.

CAUTI Risks and Patient Impact

CAUTIs make up 80% of complicated UTIs

Each year in the U.S., between 9-13k deaths caused by CAUTI complications

Each day an indwelling catheter remains, a patient has a 3-7% increased risk of acquiring a CAUTI

CAUTI is the leading cause of sepsis in patients over 65

A new approach to preventing CAUTIs

Ana Flores-Mireles is the Janet C. and Jeffrey A. Hawk Collegiate Associate Professor in Notre Dame’s department of biological sciences. Flores-Mireles began her career as a marine biologist studying genes and molecular microbiology in gray whales, before transitioning to doctoral studies in the microbiology of plant pathogens and how bacteria can force plants to produce a tumor. She quickly realized she could apply this knowledge to humans.

Smiling woman with shoulder-length brown hair and black-framed glasses, wearing a black top under a patterned tan and black jacket, posed against a white background. — Ana Flores-Mireles, a microbiologist and associate professor in Notre Dame's department of biological sciences

Gloved hands insert a long swab coated in brown material into a small labeled plastic tube as a researcher in glasses watches, blurred in the background of a lab.

As a postdoctoral researcher at WashU in St. Louis, Flores-Mireles did just that, and latched onto the problem of CAUTIs. Because of her unique trajectory, Flores-Mireles was less concerned about the microbes, which research traditionally focuses on. Instead, she wanted to understand how the environment of the bladder might be exacerbating the problem.

Flores-Mireles discovered that the inflammation that occurs by inserting a catheter was a key issue in infection. She describes it like buying a new pair of shoes for an event – without breaking them in, the friction from the shoe rubbing on the skin will cause bleeding, inflammation, and damage. So too with the catheter in a bladder. That same bleeding and inflammation brings the healing protein fibrinogen from the bloodstream to the damage site to try to repair it. These proteins are web-like and sticky in order to latch onto damaged areas, but it also means microbes can latch onto them easily, so they don’t get expelled from the bladder. As the microbes build up and colonize, infection sets in.

Flores-Mireles

“The problem is that we need [catheters], but they also predispose us to infection. So the question is, how can we make them safer? ”

She believed reducing inflammation was the key. Less inflammation would bring fewer proteins to the site, which would allow fewer microbes to adhere and infect. Rather than a vaccine or costly antibody to alter the proteins, Flores-Mireles wondered if she could instead physically prevent the fibrinogen proteins from adhering to the catheter.

“Our idea is that we need to develop something that is soft, that does not cause this damage in the bladder, but also repels these proteins so it's no longer available for these microbes to attach to,” she explained.

The result is a silicone-based oil coating added to existing catheters to give them a slippery surface so nothing can attach to it. Once dipped in the oil, the catheter can be packaged to be shelf-stable and sterile. The alterations are inexpensive – about $1 per catheter – and can be used globally, even in low-resource settings, Flores-Mireles said.

“Now, just by modifying something so simple, you don't cause inflammation, and you don't cause infection,” she said.

Coating catheters isn’t novel, she acknowledged, noting that people have long tried coating them with antibiotics with mixed results, including increased antibiotic resistance. But this coating isn’t permeated with medication. It’s just slippery and the physics of it keeps microbes from colonizing. That, she says, is revolutionary.

“What our research has done is open a new avenue where we are understanding exactly what is happening, and by understanding what is happening, we're able to target and develop efficient intervention strategies,” she said. “Everybody's really excited because there is nothing similar on the market.”

Diagram of a bladder with a catheter inserted with balloon inflated while showing a 'barrier' of silicone oil to prevent fungi and bacteria from bonding to catheter.

A researcher in a blue lab coat, safety goggles, and gloves dips a catheter into a 500mL flask containing clear silicone oil, illuminated by dramatic blue-purple laboratory lighting. — Graduate student Hope Akegbe coats a standard catheter in a silicon oil that can prevent bacterial and fungal colonization, and thus, infection.

From lived experience to lab discovery

Perhaps no one is more excited than Alyssa La Bella ’21, ’26 Ph.D.

La Bella joined Flores-Mireles’s lab as an undergraduate biochemistry major and stayed on as a doctoral candidate. During high school, La Bella had recurrent kidney stones that eventually revealed a kidney abnormality. Ultimately, she needed surgery to reroute her ureter, a process which required catheters and stents and left her prone to both bacterial and fungal infections.

Smiling woman with blond hair pulled back, wearing safety goggles, a white lab coat, and blue gloves, stands with arms crossed beside a lab bench with foil-capped flasks, bottles, and shelves of supplies. — Alyssa La Bella ’21, ’26 Ph.D.

“I was what they call a frequent flyer at the hospital. I was probably going to the hospital every few weeks and then having a surgery every couple months at that point, or if not a surgery, they were putting me under to go and look and see how I was healing and whatnot,” she said. “Infections kind of were constant. They always just seemed to be there, especially when I had the ureteral stent or a kidney stone. I was constantly on antibiotics or antifungals.”

A woman with dark-framed glasses and brown hair examines something closely in a laboratory, with blurred colorful equipment and bottles surrounding her.

Colorized scanning electron microscopy image showing a dense mixture of microbial cells in purple, yellow-green, blue, and pink against a dark background.

A woman in glasses and a gray jacket lectures at a chalkboard as students with laptops and tablets listen. A projected slide reads 'Engineered to Protect: The Fight Against Catheter Associated Urinary Tract Infections.'

Close-up of a glass flask under blue and violet light, filled with clear liquid between the 400 and 500 milliliter marks, with a curved plastic tube running down into the liquid against a black background.

When she saw Flores-Mireles was working on this problem, she jumped at the chance to be part of it.

“I sent [Flores-Mireles] an email that was just like, ‘Hey, I'm an undergraduate student here. I'm super interested in your research, not just because it's generally interesting, but also because I have experience as a urology patient with infections, and I just would love to talk to you more and see if there's an opportunity for me in your lab.’”

Flores-Mireles was brand new to the university, but as soon as her lab was up and running, La Bella was one of the first hires.

At the time, Flores-Mireles was focused on bacteria as the primary group of pathogens. It was La Bella and her personal history that opened the aperture to include fungi research. La Bella mentioned many of her own cultures revealed fungal, rather than bacterial, infections. She asked if there might be room to consider fungal pathogens. Flores-Mireles was interested, and while she didn’t have expertise in fungi, she knew someone just down the hall who could help.

Close-up of a green-capped laboratory vial and an open amber tube reflected on a blue surface, with a third tube visible in the background. — CAUTIs cause around 10,000 deaths each year in the U.S., but a new catheter adaptation has the potential to greatly reduce that number.

A gloved hand points to a region of a fluorescence microscopy image showing densely clustered cellular structures in red, green, and blue against a dark background. — CAUTIs cause around 10,000 deaths each year in the U.S., but a new catheter adaptation has the potential to greatly reduce that number.

Santiago-Tirado

Felipe Santiago-Tirado is an associate professor in the department of biological sciences who specializes in fungal pathogenesis – or how fungi are able to cause disease. He’s also married to Flores-Mireles. They met as Ph.D. students at Cornell University, and then both continued on to postdoctoral work at WashU School of Medicine. While they had considered partnering on projects before, it wasn’t until La Bella joined the lab that they had a concrete reason to collaborate.

Santiago-Tirado explained that while four of the top five causes of CAUTI are bacteria, the number two cause is a fungus, but it’s often overlooked, so much so that the papers La Bella authored in partnership with both their labs are among the first in the field. But while fungi don’t get the same attention as bacteria or viruses, Santiago-Tirado noted that because little is known about them, they are hard to treat and come with high mortality rates. His research aims to better understand how fungi cause infection and disease.

Interestingly, in the case of catheters, he found fungi like Candida albicans behave similarly to bacteria. They, too, latch onto fibrinogen proteins to create a biofilm that results in infection. The way they do it is slightly different, but the overall case is remarkably similar. The good news is that fungi, in addition to bacteria, can likely be deterred with Flores-Mireles’s silicone-coated catheters. They are now collaborating on a study for fungal CAUTIs, including Candida auris, an emergent and highly antimicrobial-resistant pathogen.

How CAUTIs affect patients and healthcare systems

Not surprisingly, there is momentum to get this catheter adaptation over the finish line. Estimates for the cost of CAUTIs range from $115 million to $1.82 billion annually. U.S. hospitals are also required to submit their incidence rates of CAUTIs to the Centers for Medicare & Medicaid Services and the Centers for Disease Control and Prevention (CDC), and the results can influence hospital ratings and medicare reimbursements.

Beyond the United States, Flores-Mireles and Santiago-Tirado are collaborating with a hospital in Mexico, where mortality rates from CAUTI are notoriously high. Eastern Europe and Asia, too, have high incidence rates. Even a slight reduction in global CAUTI incidence could save tens of thousands of lives.

Trautner

“Professor Flores Mireles’s work is more promising than anything I’ve seen in the last decade. Forward thinking work like hers moves health care into the next era of better and safer patient care for all.”

And, Trautner, the doctor from WashU said, it will lead to relief from pain and suffering, longer periods without infection, higher functioning catheters, and ultimately, “better and safer patient care.”

The results may extend beyond catheters. In time, Flores-Mireles and Santiago-Tirado could see this application working for central lines, brain stents, dialysis catheters, prostheses, and more.

“I think that medical devices in general have been one of those great medical advances that are positively affecting our society, but they have side effects,” Santiago-Tirado said. “By minimizing the side effects and still retaining the good benefits of all of these medical devices, then it's going to have a big positive impact.”

Produced by the Office of Public Affairs and Communications

Writer: Tara Hunt McMullen
Photographer: Michael Caterina

The What Would You Fight For? campaign is supported in part by a generous gift from David and Debra Delahanty.

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