In vitro evolution predicts that the IMP-1 metallo-beta-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 9.8 x 10(6) +/- 1.4 x 10(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.
Hall
Barry G
BG
Biology Department, University of Rochester, Rochester, New York, USA. drbh@mail.rochester.edu
D005075:Biological Evolution; D024881:Drug Resistance, Bacterial; D015723:Gene Library; D015378:Imipenem / Q000494:pharmacology*; D009154:Mutation / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D012706:Serratia marcescens / Q000187:drug effects / Q000235:genetics; D013845:Thienamycins / Q000494:pharmacology*; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism*
D013845:Thienamycins; D015378:Imipenem; C409201:beta-lactamase IMP-1; D001618:beta-Lactamases