Targeting superbugs

Schulte, and Zank in the Microbiology lab.UWL junior Lillian Schulte, of New Prague, Minnesota, right, works with graduate student Allison Zank in Microbiology Professor William Schwan’s lab. Schulte is a microbiology major who started conducting undergraduate research as an incoming UWL student through the Eagle Apprentice Program. This past summer she was a College of Science and Health Dean’s Distinguished Fellow.

UWL researchers — experienced and emerging — are searching for answers to a global health threat: antibiotic resistance

Antibiotic resistant bacteria are a growing, deadly problem worldwide.

At least 2 million people in the U.S. each year become infected with bacteria that are resistant to antibiotics and 23,000 of those don’t survive, according to the Centers for Disease Control and Prevention. Meanwhile, some estimates indicate more than 700,000 people globally die each year due to drug-resistant infections.

Developing new antibiotics is a key part of combating the issue. Among those fighting the battle are UWL scientists — both long-term and emerging.

Several UWL faculty formed the Mycophyte Discovery group. Over the last two decades, these professors — Aaron Monte, Chemistry; Marc Rott and William Schwan, Microbiology; Anne Galbraith, Jennifer Miskowski and Thomas Volk, Biology — have been learning about microorganisms that have the potential to cause dangerous infections in humans. They are developing new antibiotics and other anti-infectives from Native American herbal remedies and wild fungi.

Alongside them are UWL student researchers, including some incoming, first-year students and sophomores in UWL’s Eagle Apprentice Program.

“We’ve had a number of papers published that included undergraduate and graduate student authors,” says Schwan. “It’s been a big feather in the cap of these students to have contributed to peer-reviewed science.”

Emerging scientists help make new discoveries

When UWL junior Lillian Schulte stepped into Professor Schwan’s lab as an Eagle Apprentice her first year at UWL, she admits feeling intimidated. Yet, she found working at the bench alongside passionate researchers inspiring.

Zank, Schwan and Schulte pose for the camera in the lab.

From left, graduate student Allison Zank, Professor William Schwan and UWL junior Lillian Schulte. In addition to studying Staphylococcus aureus and its biofilm formation, Schwan also studies another kind of bacteria that is the No. 1 cause of urinary tract infections: Escherichia coli, among other topics.

“They really cared about what they were working on,” she says. “It was cool to be a part of that.”

One of the biggest problems Schwan’s research team was working on — and continues to work on — is an antibiotic resistant bacteria called Staphylococcus aureus. Categorized as a “serious concern” by the CDC, this species of bacteria is a major problem in U.S. hospitals where it has become the leading cause of heart valve and blood stream infections, explains Schwan who has studied this bacteria since his days working at a Washington-based biotechnology company more than 20 years ago.

Staphylococcus aureus starts as a single cell that can adhere to a surface such as a man-made device in the human body. The bacteria then multiply and create a thin film — a matrix of sugars, proteins, DNA and bacteria cells — that the body’s defenses can’t penetrate. Most antibiotics can’t get through it either.

Schwan’s research aims to more fully understand this bacterial species and how it forms a biofilm. Answers from Schwan’s lab could be passed on to develop new drugs that could stop the film formation before it starts.

Nine UWL students are working with Schwan on this and other projects this semester.

Schwan says Eagle Apprentices, though new to scientific research at the university level, share qualities such as enthusiasm and strong academics. He watches them grow most— as scientists.

“This is not like a lab course where nearly everything works,” Schwan explains. “There is a lot of failure and you have to pick yourself up by your bootstraps and solve what went wrong with your experiment. That is a good learning experience and it builds critical thinking in our students.”

“I’ve learned a lot here and I apply it in my courses,” she says. “Through that, I’ve gained a big confidence boost.”

Over the years, Schulte’s role in the lab has grown increasingly complex, and she has moved from mentee to mentor. Last year she helped a new Eagle Apprentice get acquainted with the lab. This summer she earned a Dean’s Distinguished Fellowship, continuing to research Staphylococcus aureus and biofilms.

“I’ve learned a lot here and I apply it in my courses,” she says. “Through that, I’ve gained a big confidence boost.”

Research developments involve cross-departmental collaboration

Schwan’s lab is now working to understand how a particular drug may have the potential to stop Staphylococcus aureus in its tracks before it forms the biofilm.

The promising drug has a history with UWL.

James Cook, a distinguished professor at UW-Milwaukee, took a drug discovered by UWL researchers in the Mycophyte Discovery group and changed the structure of it to create a new one with better antibacterial activity, called SK-03-92. Through subsequent testing, Schwan’s lab has found that SK-03-92 deregulates two genes that may regulate formation of the Staphylococcus aureus biofilm.

Both genes are thought to encode a two-component regulatory system, which UWL researchers believe regulates a gene involved in the production of sortase, important in the initial phase of biofilm formation.

Class aids discovery

Students in a senior level molecular biology lab (BIO 436) were also involved in the project through course embedded research.  They created mutations in the bacteria to explore this two-component system, sortase and the biofilm formation.

“Rather than just perform lab experiments and throw away the product, these students are doing something more useful,” explains UWL graduate microbiology student Allison Zank, who assists Schwan with his research and has worked closely with the class results.

Zank, who is supported by the National Science Foundation Graduate Research Fellowship Program, says the fellowship gives her the opportunity to work on an important worldwide issue while earning her graduate degree. “It is really about preventing the next major plague,” she says.

Zank has enjoyed having a diverse team in the lab, that includes incoming students. Although Schulte may have been intimidated her first day, she has ultimately been an asset, says Zank.

“She (Schulte) has been so valuable,” says Zank. “She brings enthusiasm and perseverance.”

The team is getting closer to publishing a paper that will explain how this two-component system works and how SK-03-92 is killing the bacteria.

But the discoveries happening in Schwan’s lab aren’t just in relation to antibiotic resistance.

Today, Schulte is on the pre-medicine track with goals to go to medical school and specialize in infectious disease and pediatrics.

“I’ll draw from what I’m learning now about infectious disease,” she says. “Working in the lab has solidified this is something I’m passionate about.”