DIFFERENTIAL REVERSAL OF INHIBITORY EFFECTS OF FOLIC ACID ANALOGUES ON GROWTH, DIVISION, AND DEOXYRIBONUCLEIC ACID SYNTHESIS OF MICROORGANISMS

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Abstract
The inhibitory effect (prolongation of the lag phase) of aminopterin on Candida tropicalis was substantially reversed by folic acid, but not by thymine and amino acids. Inhibition of Escherichia coli or Bacillus megaterium by aminopterin or amino-an-fol was appreciably reversed by thymine and certain amino acids, but not by folic acid or leucovorin. Cells of E. coli grown in the presence of analogue plus thymine were of normal morphology, whereas homogeneous populations of long filamentous cells were obtained with the analogue alone. In contrast, analogue plus glycine or histidine led to an enhancement of filamentation, as well as to somewhat better growth. Methylaminopterin caused no appreciable inhibition of growth of E. coli, but induced a massive development of long filaments. This selective inhibition of division was completely reversed by thymine, and partially by serine, whereas glycine and histidine still further enhanced filamentation. A lowered basophilia was associated with the analogue-induced filamentation of E. coli and nuclear elements were not clearly demonstrable in the filamentous cells. Significant decreases were found in the DNA content of E. coli grown in aminopterin, dichloroaminopterin, and amino-an-fol, whereas cells grown with analogue plus thymine (and, to a lesser extent, serine) showed a normal DNA content. Glycine or histidine did not prevent the analogue depression of the DNA value.