In vitro evolution predicts that the IMP-1 metallo-β-lactamase does not have the potential to evolve increased activity against imipenem

In vitro evolution was used to predict whether the IMP-1 metallo-beta-lactamase has the potential to evolve an increased ability to confer resistance to imipenem. Screening of eight libraries containing 9.8x10(6)+/-1.4x10(6) (mean+/-standard error) variants per library, with an average of 1.2 mutations per variant, detected no increased resistance to imipenem. The results predict, with >99.9% confidence, that even under intense selection the IMP-1 beta-lactamase will not evolve to confer increased resistance to imipenem.