Perturbation of Growth and Metabolism in Candida albicans by 4-Bromobenzyl Isothiocyanate and Iodoacetate

The inhibition by PBBI of growing Candida albicans was studied; additional information was obtained from the analysis of regeneration. The type of the growth inhibition depended on the cell suspension. At more than 107 cells per ml, the inhibition was transient; the inhibitor was taken up rapidly by the cells to a limit of 37 nmoles per mg dry wet. At higher doses, the growth was inhibited permanently, and then, and only then, a lethal effect was observed. At sublethal doses of the inhibitor, the following effects were observed: Inhibition of respiration without apprecciable .change in R.Q., of incorporation of labelled precursors into proteins and nucleic acids, and of eight of fourteen enzymes studied; the level of total free thiol groups was lowered; and a cross- over between hexose monophosphates and fructose diphosphate was induced. The original activities of the enzymes and metabolic processes inhibited were restored coincidentally with the reappearance of growth of the cells. Inhibition of G-6-PDH, PFK and of an early step in the oxidation of NAD(P)H appeared to be determinative for the growth. In the cells inhibited transiently by iodocetate, GAPDH and ADH were the most sensitive enzymes. The activity of the latter but not of the former was readily restored. The R.Q. was lowered, and was restored later than growth. The cells which recovered from the inhibition by iodoacetate appeared to be physiologically different from the control.