Inactivation of beta-lactamase from Shigella flexneri UCSF-129 by BRL 42715, a potent inhibitor

The effect of a powerful inhibitor, BRL 42715, on beta-lactamase from Shigella flexneri UCSF-129, to overcome the problem of shigellosis and its resistance to ampicillin, was studied. The I50 was determined for BRL 42715 C6-(N1-methyl-1,2,3 triazolylmethylene)penem] as 0.0049 microgram/ml being 20-fold lower than the best inhibitor, 6-beta-iodopenicillanic acid, previously reported. The MIC fell from 2,048 to 2 micrograms/ml in the presence of 1 microgram/ml of BRL 42715. The synergism of the ampicillin plus this inhibitor lasted for 9 h. BRL 42715 is an irreversible inhibitor, according to the dialysis results, and a substrate analogue.