The Fight for Safer Food

The Fight for Safer Food

To confront the threat of persistent foodborne pathogens, Steve Bowden turns to novel techniques to understand and take down those threats.

By Kyle Wong

Nearly one in six Americans suffer from foodborne illnesses each year, according to the Centers for Disease Control and Prevention (CDC). Scientists like the University of Minnesota’s Steve Bowden are working to change that.

Standard food-safety processes like pasteurization, freezing, and fermentation kill foodborne pathogenic bacteria, but these pathogens evolve to survive. Through mutation and the acquisition of new genes, pathogens can cause outbreaks from unfamiliar sources such as fresh produce, spices, and peanut butter. Bowden, an assistant professor in the Department of Food Science and Nutrition and a member of the BioTechnology Institute, is developing strategies to eliminate new and persistent pathogens.

One common offender is Salmonella, a bacterial species that infects millions of Americans each year, leading to thousands of hospitalizations and hundreds of deaths. Bowden studies how Salmonella responds to stresses in the food environments where it thrives. He seeks to identify common genetic traits that enable Salmonella to survive and grow under varied conditions. Ultimately, he hopes to develop procedures that eliminate harmful bacteria from the food system. “We want to understand why certain outbreaks occur in specific types of food and if there is a correlation with the genes found in those specific types of bacteria,” says Bowden.

To target specific foodborne pathogens, Bowden’s lab engineers a type of virus called a bacteriophage that infects and then kills bacteria. But identifying phages that work is only half the battle. Because pathogens are so diverse, effective treatment requires the right combination of phages to remove all of the pathogen targets and ensure food safety. To make things more complicated, the food matrix can also affect the phage’s efficacy. One cocktail of phages might succeed on one food but fail to remove the same pathogen in another.

Nonetheless, the Food and Drug Administration (FDA) has approved some phage cocktails. They are entirely harmless to humans and assist in the control of foodborne pathogenic bacteria during food processing. Their potential use as a safe, natural method to improve food safety is garnering interest in the food industry. Still, further research is required to enhance their efficacy and improve manufacturing methods.

Despite these challenges, Bowden’s longstanding fascination with molecular biology and microbiology keeps him motivated: “I was surprised by how many foodborne illnesses there are. I want to make use of genome sequencing to try and control these pathogens. What’s interesting about molecular biology is how we can apply it to make the world safer.”

Bowden’s drive to understand foodborne pathogens couldn’t have come at a better time. Addressing global threats to food safety, such as climate change and antibiotic resistance, requires broad thinking and a flexible approach. Bowden brings a global perspective to his work. After earning his Ph.D. in biochemistry at the University of Cambridge, he worked as a postdoc in the United Kingdom and Japan. “I feel lucky to have been in so many labs and learn different perspectives,” he says. “It’s helped broaden my appreciation for different ways to do research.”

The experience helped prepare Bowden for his research at the University of Minnesota. “The drive to understand a problem and develop techniques to study that problem has kept me in academia,” he says. “I’m excited to see what direction it takes.”

Kyle Wong is a writing intern in the University of Minnesota Science Communications Lab, majoring in Microbiology. He can be reached at wong0511@umn.edu

A Micro Lens on a Macroscopic Question

A Micro Lens on a Macroscopic Question

A Q&A with PhD Candidate Anna Bennett
By Reed Grumann 

Anna Bennett, a PhD candidate working in Trinity Hamilton’s lab, collects and studies photosynthetic bacteria that live in the extreme conditions found in Yellowstone’s hot springs. Bennett characterizes these cyanobacteria and their environment, providing data to inform evolutionary models of photosynthesis on Earth. 

How did you end up at the University of Minnesota?

At the time I began the application process for graduate school, I was working at an Air Force base in Ohio. I was researching synthetic biology with E. coli, and I knew that I wanted to get outside more, which is why I was looking into applying for environmental microbiology labs. I was accepted to study at the University of Cincinnati in the Hamilton Lab when she made the decision to move to the University of Minnesota. I decided to move too. I was really excited about her work with hot springs and extreme microbes, so it was the only lab that I interviewed with.

What stuck out to you about these extremophiles as compared to others?

I think it’s really interesting that these bacteria can perform photosynthesis. A lot of people only consider plants and a few types of algae when they think about photosynthesis, but these bacteria can do it, too. In fact, they were the first in Earth’s history to do it, but we still don’t know much about them.

Our basic question is “What did early organisms that performed photosynthesis look like?” I work to develop a better understanding of the physiology and ecology of their modern relatives to inform those evolutionary questions. 

What are the implications of your research?

The data we collect on the physiology and ecology of these cyanobacteria can be used to inform evolutionary models. To put it into broad terms, my results will help inform questions about the evolution of photosynthesis, and since photosynthesis led to oxygen on Earth, questions about the evolution of Earth as a whole. 

You work on the largest and smallest elements of biology—the environment and microbes. How do they complement each other?

Microbes are very important for large scale environmental cycles and tend to be important at the starting point of those cycles. Many of the microbes that we study fix carbon, which means they take carbon in a typically unusable form and make it usable. Since humans and animals are unable to do this for ourselves, we depend on the carbon that plants (and some microbes) fix. So microbes are critically essential for the rest of the environment. Without them we don’t have plants, we don’t have cows, and we don’t have us.

 

Reed Grumann is a writing intern in the Science Communications Lab, majoring in Microbiology and Political Science. He can be reached at gruma017@umn.edu

Synthesizing Sustainability

Synthesizing Sustainability

UMN scientists produce high-value beta-lactones from waste for use in antibiotic and anti-cancer therapies.

By: Katie Sabbia

From biofuels to antibiotics

Sustainability. It’s more than a buzzword. Recycling is a key component in a circular economy, where consumer and industrial waste become raw materials instead of landfill. University of Minnesota biochemist Larry Wackett sees high-value beta-lactones as ideal targets in a new circular economy. His laboratory works with genetically engineered strains of E. coli that convert fatty acids into beta-lactones – a key component of industrial products from pesticides to antibiotics and anti-cancer agents. Chemical synthesis of beta-lactones is painstaking and costly with yields as low as 1%. The Wackett lab’s technology could provide a reliable and efficient pipeline at a fraction of the cost.

An expert in biocatalysis, Wackett uses enzymes to transform organic compounds, whether breaking down environmental toxins or synthesizing chemicals for agriculture and industry. While working on a Department of Energy grant to develop ethanol substitutes, his lab inserted genes from soil bacteria into E. coli. They planned to use fatty acids to synthesize hydrocarbon fuels, but in the process, James Christenson, then a graduate student in the Wackett lab, made a crucial discovery.

While analyzing precursor molecules in hydrocarbon biosynthesis, he identified one intermediate molecule as a beta-lactone.

Christenson, who went on to earn his doctoral degree in Wackett’s lab, carefully isolated and identified the enzymes and other components of the chemical reactions and repeated the steps in vitro. Scientists already knew that some bacteria produced beta-lactones, but Christenson’s work revealed the biochemical mechanism by which they are created. For the first time, the beta-lactones could be made biologically by a directed process. Christenson presented his discovery at the Enzyme Mechanisms Conference in 2017 where he was sole recipient of the Founder’s Award in a competitive field of world class researchers.

“We have published a lot of papers on how to make hydrocarbons, so we did the work we set out to do,” Wackett explains. “But in the process, we discovered something else. Beta-lactones are highly valued as anti-cancer, anti-obesity, and antibiotic agents. As antibiotic resistance increases, this may be even more important than the biofuels project.”

Beta-lactones are similar in structure to the key components of antibiotics like penicillin that work by inhibiting cell wall production in the targeted bacteria. Antibiotic-resistant bacteria have evolved to resist these molecules, and rendering them ineffective. In the war on antibiotic resistance, beta-lactones could be our next line of defense.

Small molecule, big impact

“We can purify enzymes at very high yields, and we can make a lot of different structures with different properties.” To understand the structure of these complex enzymes and how they interact with other molecules, he turned to longtime collaborator Carrie Wilmot. Wilmot, an X-ray crystallographer and professor in the Department of Biochemistry, Molecular Biology, and Biophysics, helped identify the structures and mechanisms of the proteins producing the beta-lactones. Her lab produced three-dimensional models of the molecules using the diffraction patterns derived from exposing protein crystals to high energy X-rays. Viewing such models on a computer will help the team find and engineer the best enzymes to synthesize new and useful beta-lactones.

Wackett is committed to seeing his research applied outside the academic laboratory. He and his co-workers filed a patent for the process which can be used to make beta-lactones with different properties and ideally, some will be useful as drugs to treat cancer or bacterial infections.

With a seed grant from the MnDRIVE Environment Initiative, Wackett is partnering with Minnesota-based life science firm Bio-Techne to look at commercial processes for producing beta-lactones. The ultimate goal is to develop a key component of the circular economy: converting wastes to high value products.

Katie is an Industrial & Systems Engineering major in the University of Minnesota’s College of Science and Engineering and an intern in the BioTechnology Institute’s Science Communications Training Program

Photo taken by Mikaela Armstrong. Mikaela is a Graphic Design major in the University of Minnesota’s College of Design and an intern in the BioTechnology Institute’s Science Communications Training Program

Engineering a self-cleaning environment

Engineering a self-cleaning environment

UMN researchers create self-cleaning Biohubs to mitigate the impact of pollutants in Minnesota’s waterways

by Lauren Holly

Minnesota’s Iron Range is dotted with active and abandoned mining sites. Left untreated, runoff from these sites can flow into the environment and release heavy metals and organic pollutants, ultimately endangering wildlife and threatening human health.

But what if we could engineer the environment to clean itself? With support from the MnDRIVE Environment initiative, researchers in the BioTechnology Institute’s Schmidt-Dannert lab are developing Biohubs using genetically engineered proteins capable of breaking down heavy metals and removing toxins from mine drainage and other industrial sites.

Biohubs take advantage of a protein’s natural tendency to self-assemble into stable shell-like structures. Their porous surface converts harmful metals and organic pollutants into non-toxic components.

Based on similar structures found in nature, the lab’s model Biohub converts toxic mercury compounds into a form that can be released safely in the environment. The process relies on modified proteins that bind toxins while enzymes, small proteins capable of catalyzing biochemical reactions, convert mercury to its inert elemental form. The system is “self-cleaning” because the enzymes remain active inside the Biohub until it encounters the next metal, and restarts the process.

On-site, the Biohubs are placed in glass or metal columns that act as a filtration system; contaminated water enters through one end of the column and exits at the opposite end of the column free of toxins.

Using enzymes to clean the environment has advantages. They are versatile and leave no toxic residue, but enzymes found in nature are not always stable, and Schmidt-Dannert’s team needed a way to protect and stabilize the proteins. Enter Minnepura Technologies; a biotech startup co-founded by University of Minnesota Professors Alptekin Aksan and Lawrence Wackett. Minnepura specializes in the development of biocomposite materials designed to encapsulate and protect proteins. Minnepura and will encase the Biohubs in an easily adaptable, light-weight silica that supports the structure over time.

“Initial studies will focus on remediation of heavy metals from mine drainage, but the system could also be applied to clean up of pesticide-contaminated soil or water near agricultural land,” explained Maureen Quin, a lead researcher on the project.

Schmidt-Dannert believes engineered proteins hold considerable potential as a platform technology for sustainable bioremediation. “If we can get this to work with organic compounds, this solution could be very versatile and able to convert a variety of different pollutants.” In states like Minnesota trying to balance the competing demands of industry and environmental stewardship, Biohubs may help the environment clean itself.


Lauren Holly is an intern in the BioTechnology Institute’s Science Communications Training Program.

Minnesota Lakes in Peril

Minnesota Lakes in Peril

UMN researchers use DNA technology to track fecal contamination in Minnesota waters

View the full infographic here.

By: Rachel Zussman
Infographic by: Kate Johns

Imagine your next summer vacation: boating, fishing, or swimming in Minnesota lake country. After months of anticipation, you arrive at the lake to find the beaches closed and the water contaminated by fecal bacteria. Unfortunately, it’s not an isolated occurrence. According to the Minnesota Pollution Control Agency, 40% of Minnesota’s lakes and streams are impaired, with fecal contamination becoming a growing concern. A team led by University of Minnesota microbiologist Michael Sadowsky hopes to provide public health officials with better tools to track the source of contamination and assess the public health risk.

Fecal contamination has been a national issue for decades. In 1977, the US government adopted the Clean Water Act using coliform bacteria (and later the bacterium E. coli) as an indicator for fecal contamination of waterways. Commonly found in the intestinal tract of the warm-blooded animals, E. coli in the water suggested the possible presence of other fecal pathogens, and forced officials to close beaches out of an abundance of caution. As new research indicated that E. coli could survive in nature outside the gut, its value as an indicator of water quality waned. Researchers now focus on the source of bacteria to better assess the public health risks and eliminate contamination at the source.

Initially, Sadowsky’s team relied on a technique known as DNA fingerprint analysis to identify the source of fecal contamination. “We would go into the environment and collect ‘fingerprints’ of individual bacteria,” explains Sadowsky. “These ‘fingerprints’ would then be matched with E. coli bacteria obtained from feces of 17 animal species.” Though more accurate than older methods, DNA fingerprinting only worked about 75% of the time.

Improvements in DNA sequencing technology now allow Sadowsky’s team to analyze fecal samples from a large number of animal species. Using SourceTracker, a software program developed by the UMN’s Knights Lab, the team can compare the distribution of organisms in water samples with those found in the animals.

So far, Sadowsky has successfully identified contamination coming from a few sources. But since contamination often comes from both humans and animal origin, making the source of the contamination harder to identify and remediate.

Though wildlife and agriculture add to the problem, Sadowsky believes that both point and non-point source microbial contamination are symptoms of urbanization. “We have cities with millions and millions of people,” he adds. “Every time you flush a toilet, that water has to go somewhere.”

As the technology continues to improve, Sadowsky hopes the research will help inform public policy. “I want to work with decision-makers to establish water quality standards based on the source of contamination.”

Health risks depend on both the source and the level of fecal contamination. With better tools at their disposal, policymakers can continue to protect the public while residents and tourists continue to enjoy summer days on Minnesota’s 10,000 lakes.

Rachel Zussman is a Biology, Society, and Environment major at the University of Minnesota’s College of Liberal Arts and an intern in the BioTechnology Institute’s Science Communications Training Program.

Katie Johns is a recent graduate with a major in Graphic Design from the University of Minnesota’s College of Design, and an alumni of the BioTechnology Institute’s Science Communications Training Program

Saving Little Brown Myotis

Saving Little Brown Myotis

Can native microbes help protect Minnesota’s bat population from the deadly white-nose bat syndrome?

By: Kelley Hosieth
Infographic: Megan Smith

View full infographic here.

Pseudogymnoascus destructans (PD), the fungus responsible for white-nose syndrome (WNS), was first detected in upstate New York in 2007. Over the past decade, that state’s bat populations have declined by 90% and the fungus has since spread across the country, including Minnesota.

To combat the spread of WNS, the University of Minnesota’s Christine Salomon and her research team have been working in the Soudan Mine, an old iron mine in northern Minnesota. They hope to find native fungi or bacteria that act as a biological control to stop PD from causing more ecological damage.

“A biological control is a good solution because it spreads like the disease and can be dispersed into the environment,” says Michael Wilson, a postdoc in the Salomon lab. “That sounds like a simple plan, but nothing like this has ever been done before.”

The terrain produces one of the greatest challenges for scientists. Bats are widely dispersed in dark caves with uneven terrain. Sometimes, researchers don’t know how large the caves actually are.

WNS spreads when infected bats come into contact with healthy bats. The fungus infects bats’ skin, which causes them to wake up more frequently from hibernation. Once awake, the bats quickly burn their stored fat, and they starve.

Wilson is working on the basic biology of P. destructans to help guide the implementation of a biological control strategy. “If it only affects bats, and all the bats die, then the environment will be disease-free,” Wilson says. “But if the pathogen is self-sustaining, the environment is contaminated indefinitely.”

Some researchers have argued for no intervention to save little brown bats, (Myotis lucifugus) and their larger cousins, northern long-eared bats (Myotis septentrionalis). They believe that resources should go to saving the remaining 10% of bat populations that survived infection.

“It would require a big investment in protecting remnant populations. So you can either intervene now or use all your resources to try and help the remnant populations survive– even if we don’t understand why they survive,” Wilson said.

Salomon, a member of the University’s BioTechnology Institute continues to work on white-nose syndrome, testing hundreds of fungal and bacterial isolates that have the potential to act as a biological control. Once the lab identifies the most promising strains, they’ll begin preliminary testing of control agents on surfaces in the field.  They are hopeful they have an effective method to help bats in Minnesota and across the country. Although they would like to spend many more years refining and testing their biocontrol candidates in the lab, time is running out due to the precipitous decline in bat populations every winter.  “There are so many questions that cannot be answered until we do field trials,” says Salomon. “There are risks that come with it but that’s part of our work.”