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Predicting Superbugs' Countermoves to New Drugs

A leading cause of skin and wound infections once confined largely to hospitals and nursing homes, methicillin-resistant Staphylococcus aureus, or MRSA, is now cropping up in schools, farms and locker rooms, infecting otherwise healthy people.

Researchers have used a program called OSPREY to predict how MRSA will adapt to a new experimental drug ahead of time, before the drug is tested on patients.

Credit: Lei Chen and Yan Liang

Duke University researchers have developed OSPREY, software that can predict a constantly evolving infectious bacterium's countermoves to new drugs before the drug is tested on patients.

They used the software to identify the genetic changes that will enable methicillin-resistant Staphylococcus aureus (MRSA) to develop resistance to a class of new experimental drugs that show promise against the disease.

Developing preemptive strategies while the drugs are still in the design phase will give researchers a head start on the next line of compounds that will be effective despite the germ's resistance mutations. "If we can somehow predict how bacteria might respond to a particular drug ahead of time, we can change the drug, or plan for the next one, or rule out therapies that are unlikely to remain effective for long," says Duke's Pablo Gainza-Cirauqui.

The researchers used OSPREY to identify DNA sequence changes in the bacteria that would enable the resulting protein to block the drug from binding, while still performing its normal work within the cell. The researchers treated MRSA with the new drugs and sequenced the bacteria that survived, and found more than half of the surviving colonies carried the predicted mutation that conferred the greatest resistance.

From Duke University News
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Abstracts Copyright © 2015 Information Inc., Bethesda, Maryland, USA


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