A new software program called OSPREY has shown promise in predicting drug resistant mutations in response to early-stage leads. Researchers at Duke University and the University of Connecticut used the OSPREY software to identify and predict the genetic changes that allow methicillin-resistant Staphylococcus aureus (MRSA) to develop resistance against new experimental antibiotic medications. The program’s algorithm correctly predicted two of the genetic changes that occurred after the live MRSA bacteria were treated with propargyl-linked antifolates that bind and inhibit a bacterial enzyme called dihydrofolate reductase (DHFR). Afterwards, the bacteria that survived was sequenced and more than half of the surviving colonies carried the predicted mutation that reduced the drugs’ effectiveness by 58-fold. The software is now being used to predict resistance mutations to other medications used to treat pathogens like E. coli and Enterococcus.

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