MUTATION TO NEOSTIGMINE RESISTANCE IN A CHOLINESTERASE-CONTAINING PSEUDOMONAS

Abstract

In a strain of Pseudomonas fluorescens containing an inducible cholinesterase, the activity of that enzyme is rate-limiting for growth when acetyl-choline is the sole source of carbon or nitrogen. Under these circumstances, neostigmine, a cholinesterase inhibitor, becomes a growth inhibitor. A neostigmine-resistant mutant was isolated, and the properties of its cholinesterase were compared with those of the wild-type enzyme. There were no differences in penetration of cells by inhibitor, rate of enzyme-inhibitor combination, affinity of inhibitor or substrate for the cholinesterase, or protective effect of substrate upon the enzyme. However, the mutant consistently formed cholinesterase at about twice the wild-type rate. Mutation, in this case, appears to result in a specific change in the differential rate of enzyme biosynthesis. The relationship of this change to neostigmine resistance is discussed, and it is suggested that the effect observed here may be prototypic of a general type of mechanism responsible for acquired drug resistance.