EFFECT OF FOLIC ACID ANALOGUES ON GROWTH AND CELL DIVISION OF NONEXACTING MICROORGANISMS

Abstract

The effects of 6 analogues of folic acid on growth and division were studied with a variety of microorganisms nonexacting for folic acid. The inhibitory action of the analogues was markedly lower in complex organic media than in simple, chemically defined media. The lag phase with Candida tropicalis was greatly prolonged by some of the analogues, but recovery occurred (except from dichloroaminopterin) on continued incubation. Recovery from aminopterin results from enzymatic inactivation of the analogue, involving a cleavage (presumably reductive) of the molecule, and the accumulation of butanol-soluble free pteridine within the yeast cells. Nonproliferating cells of C. tropicalis cleave aminopterin with the liberation of a diazotizable, aromatic amino compound (p-aminobenzoyl-glutamic acid residue). In Escherichia coli extremely long filamentous cells (50-100[mu]) were produced in 10-5 M concentration of aminopterin, amino-an-fol, or methylaminopterin. These filamentous cells had little affinity for basic dyes, and nuclear elements were poorly defined. The bearing of these findings on the mode of action of folic acid analogues is discussed.