Effect of Aculeacin A, a Wall-Active Antibiotic, on Synthesis of the Yeast Cell Wall

Abstract

A wall-active, amphophilic antibiotic, aculeacin A, significantly but incompletely inhibited in vitro the activity of .beta.-1,3-glucan synthase prepared from highly susceptible yeasts Saccharomyces cerevisiae and Candida albicans. Comparable cell-free preparations from S. cerevisiae active in chitin synthase or mannan synthase were insensitive to the antibiotic, suggesting selectivity of its action in synthesis of the yeast cell wall. An EM study of the effects of aculeacin A at 0.31 .mu.g/ml, the optimally active concentration, on osmotically stabilized C. albicans cells revealed morphological alterations in both cell walls and cell membranes. Deformation in contour and derangement of the layered structure of the cell wall were prominent. Massive fibrous material of .beta.-glucan-like microfibrils was occasionally extruded from the cell surface. Accompanying this effect on the cytology of the cell wall, ultrastructural and functional impairment of the cell membrane was demonstrated by transmission and freeze-fracture EM techniques. These data suggest that aculeacin A affects synthesis of the yeast cell wall through not only selective blockage of .beta.-1,3-glucan synthase, as a result of a primary interaction with the cell membrane, but also inhibition of the fabrication of .beta.-glucan or other wall components into well-organized cell walls.