Differential reversal of inhibitory effects of folic acid analogues on growth, division, and deoxyribonucleic acid synthesis of microorganisms.

Many methods are now available for achieving selective inhibition of cellular division among a variety of microorganisms. A few reports are available presenting analyses of the composition of bacterial cells grown in the absence of cell division. It was shown by Nickerson and Sherman (1952) with Bacillus cereus that homogenous populations of greatly elongated cells (devoid of interior partitions) could be obtained by the magnesium-deficiency technique of Webb (1948) in crop yields nearly identical with normal, control cultures. Furthermore, the total nitrogen per unit weight was identical in filamentous and normal cells. The RNA3 content of filamentous cells of B. cereus was shown to be similar to that of normal cells and Webb (1953) has shown the RNA and DNA3 contents per "unit cell" of normal and filamentous cells of Clostridium welchii to be closely similar. In the latter work, results achieved with the Feulgen staining technique accorded well with the analytical data for DNA content, i. e., Feulgen positive elements were spaced at "unit cell" intervals along the length of a filamentous cell. In the work reported in the present paper, low concentrations of certain folic acid analogues are shown to inhibit division to a greater extent than they inhibit growth. Filamentous cells resulting thereby were without clearly demonstra-