Electron‐microscopic and biochemical studies on morphological changes in Staphylococcus aureus following exposure to protein synthesis inhibitory agents such as lincomycin (LCM), clindamycin (CLM), erythromycin (EM), and spiramycin (SP) are presented in this paper. It was demonstrated that bacterial cell walls became extremely thickened usually with the formation of multilayers, when exposed to each of the above‐mentioned antibiotics. Furthermore, electron density of the cytoplasm was higher in those cells exposed to drugs than in intact control cells. Incorporations of 14C‐labeled l‐lysine into the cell‐wall fraction and the protein fraction were measured for biochemical elucidation of these phenomena. Labeled lysine was selectively incorporated into the cell‐wall fraction when the test organism was exposed to the respective antibiotics. Uptake at 15 min after exposure was about twice as large as that of intact control cells. SP and CLM inhibited protein synthesis while they stimulated cell‐wall synthesis. The evidences for thickening of, and formation of multilayers in the bacterial cell walls following exposure to drugs were closely related to the stimulating action of these antibiotics on the cell‐wall synthesizing system. Morphology of resistant clinical isolates following such antibiotic exposure was also investigated using two staphylococcal strains, one resistant to EM alone and the other completely cross‐resistant to all the macrolides.
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Nαkαo et al. (1972) studied this question.