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Scientists notch a win in war against antibiotic-resistant bacteria
Date:2/4/2013

currently understand E. coli metabolism. Collins' team began by adding to this "system-level" metabolic model hundreds of reactions that are known to increase ROS production. Then they deleted various genes to see which were involved in ROS production, honed in on the suspected targets after running thousands of computer simulations, and validated the model in the laboratory -- achieving 80-90% agreement with the model-based predictions.

"The next challenge was to determine if increasing the ROS production by the cell itself would render it more susceptible to death by oxidative, ergo, antibiotic attack," Collins said -- and it did. The team deleted a series of genes that led to increased ROS production in the cell, added different antibiotics and biocides such as bleach known cell-killers by way of increasing ROS production and the cells died at a much higher rate than the cells without the deleted genes. In short, by interfering with the bacterial metabolism, the antibiotics and biocides were even more lethal to the cells.

"There is no magic bullet for the global health crisis we're experiencing in terms of antibiotic-resistant bacteria," said Don Ingber, M.D., Ph.D., Wyss Founding Director, "and yet there is tremendous hope in the kinds of pioneering systems biology approaches Jim and his team are spearheading."

The team's next steps are to use molecular screening technologies to precisely identify molecules that boost ROS production, Collins said, and to test the approach used in this E. coli study on other kinds of bacteria -- such as the mycobacteria responsible for tuberculosis, a potentially lethal lung disease.


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Contact: Kristen Kusek
kristen.kusek@wyss.harvard.edu
617-432-8266
Wyss Institute for Biologically Inspired Engineering at Harvard
Source:Eurekalert  

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Scientists notch a win in war against antibiotic-resistant bacteria
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