BYLINE: Jeni Bushman, School of Molecular and Cellular Biology

Newswise — The human body is a stressful place for bacteria to live. They must defend against many chemical and physical stressors, in addition to the immune system. One major physical stressor is fluid flow, which constantly circulates in the bloodstream, urinary tract, and lungs. Research has traditionally ignored the impact of flow on bacteria because it is challenging to model in laboratory settings. A new study from the lab of , assistant professor of biochemistry at the University of Illinois Urbana-Champaign, explores how physical flow and chemical stressors combine to inhibit pathogenic bacteria. Their findings, published in , shed light on the dynamics of bacterial infections.

Doctors and engineers consider fluid flow every day when calculating how quickly an IV drip will circulate through a patient or designing a pipeline system. For biologists, studying flow is challenging because the tools commonly used in research — like test tubes and Petri dishes — aren’t conducive to creating real-life flow environments. But the Sanfilippo lab takes an interdisciplinary approach using a combination of biology, chemistry, physics, and engineering to investigate how physical stressors impact bacterial cells. By constructing microfluidic devices—tiny platforms designed to recreate flow at the cellular level—the researchers mimic the movement of fluid through the human body. By connecting these devices to a syringe and pump, they generate realistic flow environments to study how bacteria respond under stress.

 from Sanfilippo’s lab uncovered the identity of a chemical compound that influences bacterial response through fluid-flow interaction. After identifying hydrogen peroxide as the chemical compound, the lab members began examining its effect on bacterial physiology. In the current paper, they discover that combining flow and hydrogen peroxide synergizes to block bacterial migration and growth of the human pathogen Pseudomonas aeruginosa.

Hydrogen peroxide is naturally present in the human body in tiny amounts about 100,000 times less concentrated than what’s found in the familiar brown bottle sold in drug stores. Sanfilippo and his colleagues discovered that in flow, the amount of peroxide required to inhibit bacterial growth is almost exactly the amount found in the human body.

“The most surprising part of our paper was the discovery that previous research lacking flow vastly overestimated the amount of hydrogen peroxide needed to inhibit bacteria,” said Anu Sharma, a PhD student and first author of the paper. “We learned that under host-relevant flow conditions, flow increases hydrogen peroxide effectiveness 50-fold, allowing natural levels of hydrogen peroxide to block bacterial migration and growth.”

The researchers were also interested in exploring the outcome of different combinations.

“When you combine stressors, you can get unpredictable results,” Sanfilippo said. “For example, depending on the interaction effects, stressors could exhibit additive properties (2+2=4), negative synergy (2+2=3), or positive synergy (2+2=5). In our paper, we discovered a situation with clear positive synergy, as flow and hydrogen peroxide combined to generate a response that was much stronger than the sum of their individual effects.”

Their results now beg the question: How do other combinations of stressors impact bacteria? Using microfluidic systems that model host situations, the Sanfilippo lab plans to continue to investigate how harmful bacteria overcome the stress of the human body.

The paper, “Combining multiple stressors blocks bacterial migration and growth,” was published in Current Biology and was supported by the National Institutes of Health.