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Published June 11, 2011, 12:00 AM

Bacteria busters: NDSU E. coli research targets biofilm growth

Work has practical implications for food safety, medical devices
FARGO – Bacteria are a social bunch. They spend most of their lives in multilayered colonies called biofilms, taking up residence on everything from teeth to medical supplies to food processing equipment.

FARGO – Bacteria are a social bunch.

They spend most of their lives in multilayered colonies called biofilms, taking up residence on everything from teeth to medical supplies to food processing equipment.

They’re tough to evict, and they can make people sick, sometimes fatally.

North Dakota State University researchers led by Birgit Pruess are exploring ways to wipe out those colonies or stop them from forming in the first place.

Pruess, an assistant professor of bacterial physiology in NDSU’s Department of Veterinary and Microbiological Sciences, hopes the research will eventually lead to a spray-on liquid that, among other applications, will reduce E. coli cases such as the deadly outbreak in Germany, her native land.

“The shorter-term goal of our research is to identify the chemicals that inhibit and support biofilms and to understand gene regulation – which genes are turned on and off, which ones are important in biofilm formation – so that we can propose those as drug targets,” Pruess said.

The North Dakota Beef Commission and state Board of Research and Education are among those funding the research.

“So I have been able to sell it to farmers to a certain extent,” Pruess said.

Nancy Jo Bateman, the commission’s executive director, said producers want to ensure their beef is safe for consumers, but they lose that control as soon as their cattle leave the ranch.

“If there’s some wonderful new process that could be implemented in the beef production chain that will make our product even safer than it is right now, we’re certainly going to be advocates for that,” Bateman said.

Unlike antibiotics, which inhibit bacterial growth but also may promote the formation of drug-resistant strains, Pruess is trying to affect signal transduction – how bacteria communicate – by introducing different nutrients to the bacteria.

“They’re mostly being offered something that they would consider food, but then it affects them in some ways that they would do something that’s less harmful to us,” she said.

Philosophy changes

Between 60 percent and 80 percent of all bacterial infections involve biofilms, according to the National Institutes of Health and the Centers for Disease Control and Prevention.

However, while biofilms are common, they’re also difficult to study.

“In the past, we’ve always grown bacteria right in the flask, because it’s easy and a pure culture and they’re controlled conditions, but they don’t really live that way,” Pruess said.

Understanding of biofilms has increased in the past 15 years, accompanied by a change in philosophy.

“Initially, there was some push into trying to figure out whether there are any genes that are specific to biofilms,” Pruess said. “And it seems like that’s not the case, that it’s more an output of general metabolism overall.”

In other words, everything in the cell is interconnected, and it’s more of a network of gene regulation and metabolism.

“And biofilm is an output of the entire thing, and not just of a specific pathway,” Pruess said. “It’s hooked up to everything that’s going on in the bacteria, and that is of course more difficult to investigate.”

To overcome that brain buster, associate professor Anne Denton in NDSU’s Department of Computer Sciences developed algorithms to help mine the complex data being produced by the research.

Pruess is studying the data to identify which nutrients affect how biofilms assemble so that biofilms can be prevented or treated – or harnessed, in the case of beneficial biofilms such as those used to produce bio­fuels.

Practical applications

With a $358,750 grant from the NIH, the research could someday lead to the design of biofilm-resistant materials for medical equipment such as cath­e­ters, as well as drugs that target biofilms.

Biofilms are three-dimensional, so not all of their bacteria behave in the same way. Those in the outer layers receive more nutrients and oxygen but are also more exposed to antibiotics and immune system responses, whereas the inner bacteria receive fewer nutrients but are more protected from attempts to remove them, Pruess said.

In the past, researchers studied gene regulation of biofilms by scraping bacteria off a surface, mixing them together, testing them with a control agent and averaging their re­sponses. But NDSU re­searchers use a newer technique that involves attaching fluorescent markers to the control agent to see visually how and where genes express themselves, Pruess said.

“And then we could say, OK, the ones that get expressed early may serve as a target for new prevention techniques, whereas the ones that get expressed late but it’s the outside of the colony, those could serve as targets for new drugs,” said Pruess, who will become an associate professor in August.

Preeti Sule, a doctoral student at NDSU, has tested a harmless strain of E. coli on meat and found that a certain regulator protein affects cell division and biofilm formation. By affecting the amount of the regulator, researchers hope to manipulate the bacteria into a behavioral response more to their liking. In the case of meat, that means reducing cell division so there are fewer bacteria, Pruess said.

However, it takes only 100 harmful E. coli bacteria to make a person sick, “so even if you would reduce it by quite a bit, I mean, getting below 100 would always be tricky,” she said.

The results of NDSU’s research were recently published in the journal Applied and Environmental Microbiology, and they could be helpful to those dealing with the outbreak overseas, Pruess said.

It could be a decade before an anti-biofilm spray, which would be developed by someone outside of NDSU’s lab, is ready to submit for federal approval, she said.


Readers can reach Forum reporter Mike Nowatzki at (701) 241-5528

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