CYTOLOGICAL ASPECTS OF ANTIMICROBIAL ANTIBIOSIS. III. CYTOLOGICALLY DISTINGUISHABLE STAGES IN ANTIBIOTIC ACTION OF COLISTIN SULFATE ON ESCHERICHIA COLI.

Kaye, Jeremy J. (Cornell University Medical College, New York, N.Y.) and George B. Chapman. Cytological aspects of antimicrobial antibiosis. III. Cytologically distinguishable stages in antibiotic action of colistin sulfate on Escherichia coli. J. Bacteriol. 86:536-543. 1963.-Broth cultures of Escherichia coli were subjected to a constant concentration of colistin sulfate for varying periods of time. Controls and treated cells were fixed, dehydrated, and embedded in methacrylate, and ultrathin sections were examined in an electron microscope. Three stages in the antibiotic process were discerned. Stage 1 was characterized by a disruption of the axial orientation of the nuclear material and by an invasion of nuclear areas by tufts of material presumably of cytoplasmic origin; no loss of cellular contents could be detected cytologically. Stage 2 was characterized by the loss of nuclear material and by a loss of typical cytoplasmic granularity, an increase in cytoplasmic electron density, and an agglomeration of the cytoplasm into packed tufts of material; in contrast to the nuclear material, there was no loss of cytoplasmic material in this stage. Stage 3 was characterized by the loss of the altered cytoplasmic material but with the persistence of mesosomes, plasma membrane, and cell wall. Speculation that each and all of these changes might have resulted from an altered intracellular milieu secondary to a primary effect of the antibiotic on the plasma membrane is presented.