Antibiotics Off the Beaten Path

As more antibiotic-resistant “superbugs” emerge, it’s clear that we desperately need new antimicrobial drugs. Yet, over the past couple of decades, antibiotic discovery has largely been stagnant.

“The reality is there’s almost no new antibiotics that are developed. And that’s because pharmaceutical companies have decreased their investment—in part because of the rediscovery issue,” explains bacteriology professor Cameron Currie.

The “rediscovery issue” refers to the fact that soil has historically been the prime source of new antibiotics—but it seems to be tapped out. When scientists screen soil microbes for new antibiotics, they keep finding the same compounds over and over again.

Currie is part of a team that is looking elsewhere.

Currie and his colleagues have been focusing their efforts on microbes that are associated with insects, plants and marine life from all around the United States, funded by a $16 million grant from the National Institutes of Health that was awarded in 2014.

“One of the major hurdles is finding new compounds, and that’s where we’re really excelling,” says Currie, a co-principal investigator on the grant. His partner is David Andes in the UW–Madison School of Medicine and Public Health.

At the front end, the work involves some good old-fashioned bioprospecting. Currie’s group, which is in charge of the terrestrial sphere, has gathered more than 2,000 flies, aphids, caterpillars, bees, ants and other insects, as well as mushrooms and plants, from locales near and far, including Alaska, Hawaii and Wisconsin’s Devil’s Lake.

Back at the lab, things get high-tech pretty quickly. Microbes are isolated from the samples and tested for antimicrobial activity. Promising strains undergo genetic sequencing that allows Currie’s group to determine how likely they are to produce novel antibiotic compounds. From there, other scientists involved in the grant go on to test the most promising compounds in a mouse model of infection. This approach has already yielded some exciting drug candidates.

“We have 9,000 strains to screen, and we have already found some new compounds that are effective at combating infections in mice and have low toxicity,” says Currie.

With so many samples to process, Currie’s group adopted bar code technology to help them keep track. They have a bar code reader—like you’d find in a grocery store— connected to a lab computer that they use to scan petri dishes, look up samples and add new data. For each microbial strain they’ve isolated, the database has photos of the “host” insect or plant, GPS coordinates for the collection site, assay results, genetic sequence and much more.

At this point, Currie feels confident that the project will pay off, and he’s eager to see one of the group’s compounds go into human clinical trials.

“If you find one new antibiotic that gets used in treatment, it’s a major success. You’re saving people’s lives,” Currie says.

Tasty Solution

After having a stroke in 2008, Jan Blume lost the ability to swallow for two full years. As she slowly regained that vital function, she faced a new challenge: drinking the thickened beverages that are recommended for people with swallowing problems, or dysphagia. She found the drinks almost intolerable.

“They taste bad and the texture is so weird,” recalls Blume, a retired nurse living in Appleton who can now eat and drink whatever she wants. “At some point, I would have just stopped using them—and either done okay or developed problems.”

Fortunately there may soon be a better beverage option for people with swallowing problems, thanks to collaboration between a dysphagia specialist at the UW–Madison School of Medicine and Public Health—and a candy expert at CALS.

It started by chance when JoAnne Robbins, head of the medical school’s Swallowing, Speech and Dining Enhancement Program, asked CALS food scientist Rich Hartel if she could borrow his viscometer, a device that measures viscosity, or the thickness of fluids.

“After learning that one of Rich’s areas of expertise was chocolate, I mentioned that there are all these awful-tasting drinks made for people with swallowing problems, and nothing in chocolate,” recalls Robbins, a professor of medicine with an affiliate position in the CALS nutritional sciences department. “So we decided to develop a thickened chocolate drink together.”

The biomechanical events of swallowing are complex, involving 40 sets of muscles. Many things—including injury, illness and natural muscle atrophy due to aging—can cause dysphagia, which afflicts some 18 million adults in the United States.

The condition can be embarrassing. Some people with dysphagia simply stop going to restaurants or even eating with their families at home due to the struggle to swallow or the length of time it takes them to finish a meal. “This can have a devastating impact on social structures,” says Robbins.

But it’s more than just a quality-of-life issue, notes Robbins. Dysphagia can cause dehydration, hunger and malnutrition. Worse, if people with dysphagia aspirate liquids or food into their lungs, it can lead to pneumonia—and possibly death.

Many patients with dysphagia are advised to drink thickened beverages, which tend not to leak into the airway. But these products often leave much to be desired, and not just because of a bad flavor.

“The commercial products that are out there don’t match the diagnostic standards. So people think they’re buying a ‘nectar thick’ beverage, which is supposed to be a certain viscosity, but it’ll turn out that it’s not even close,” says Hartel.

That’s where Hartel and Robbins figured they could help: by developing what they call “bio-
physically based fluids” that match the diagnostic standards—making them safer for patients to drink—and that also taste good.

With the support of a U.S. Department of Agriculture grant, Hartel analyzed 15 thickeners and developed beverages using a handful of them. Robbins tested the drinks for safety in her patients, and a third team member, University of Minnesota researcher Zata Vickers, gathered key sensory data.

Ultimately the team gave up on chocolate after reading a number of studies showing that citrus flavors elicit a faster, better swallow. They are in the process of patenting their beverage technology through the Wisconsin Alumni Research Foundation, and are excited for the day when people who must drink thickened beverages—as Jan Blume did—will have a safer, tastier option.

“I’m in this to make my patients feel better,” says Robbins. Of her CALS collaborator Robbins says, “Rich is a very good partner. He was open to expanding the focus of his research program. He liked the idea of helping people directly.”