Cystic fibrosis patients may breathe easier, thanks to bioengineered anti...(searchers then developed a computational...)

Date:9/25/2007

searchers then developed a computational model to mimic the biological system. The model accurately predicted the structure of the actin-lysozyme bundles, and agreed quantitatively with the small-angle X-ray scattering experiments, said Erik Luijten, a professor of materials science and engineering, and of physics, as well as a researcher at the Beckman Institute and the other corresponding author of the PNAS paper.

The next step was to find a way to liberate the lysozyme, or prevent it from binding in the first place. Using their model, the researchers explored the consequences of varying the positive charge on the lysozyme.

When we reduced the charge, we found a huge effect in our model, Luijten said. The lysozyme would not bind to the actin. It floated around independently in the mucus.

Then, through genetic engineering, the researchers made lysozyme with roughly half the normal charge. Experiments confirmed the simulations; the reduced charge prevented lysozyme from sticking to actin, without significantly reducing the all-important antimicrobial activity.

Although much work remains, future cystic fibrosis patients might use an inhaler to deliver genetically modified charge-reduced antimicrobials to upper airways. There, these non-stick antimicrobials would go to work killing bacteria, and mitigate against long-term infection.

The implications of this research extend into other areas as well. In water purification, for example, one of the steps involves putting positively charged molecules in the water to grab negatively charged pollutants. The resulting aggregates settle to the bottom of holding tanks and are removed from the water supply.

A better understanding of how oppositely charged molecules bind in aqueous environments could lead to ways of removing emerging pathogens in water purification, Wong said.

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Contact: James E. Kloeppel kloeppel@uiuc.edu 217-244-1073 University of Illinois at Urbana-Champaign Source:Eurekalert

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