Observations by phase microscopy showed that Salmonolla typhosa located within L929 mouse fibroblast cells multiplied at the same rate as extracellular organisms; i.e., they divided about every 30 min.
Multiplication of S. typhosa ceased promptly when streptomycin, chloramphenicol, penicillin or synnematin was added to infected tissue cultures. Moreover, division of extra- and intracellular organisms stopped simultaneously. Thus, for the first time it was demonstrated directly that antibiotics which penetrate mammalian cells retain their biologic properties.
Penicillin and synnematin induced spheroplast formation in those bacilli situated extracellularly but not in those located within healthy L cells. Intracellular spheroplast formation was observed in dying cells or in cells the permeability of which was irreversibly altered by addition of saponin. Chloramphenicol and streptomycin did not exert a marked effect on morphology of the bacilli.