Morphology of Escherichia coli Exposed to Penicillin as Observed with the Electron Microscope.

The morphological effects of penicillin on gram-negative nonsporeforming rods, especially E8cherichia coli, have been studied by several authors. Gardner (1940) reported that grotesque forms of E. coli resulted from autolytic swelling when this organism was treated with penicillin and that elongated, swollen cells resulted from incomplete fission. Weiss (1943) showed by electron micrographs that certain bacterial cells, when medicated with penicillin, became enlarged and fission was often incomplete. The effects of penicillin on intestinal bacteria as reported by Thomas and Levine (1945) included long twisting filaments in lower inhibitory concentrations and cells resembling Pasteur flasks, swelled fusiform rods, large globular cells, and irregular masses in higher concentrations. In concentrations just above those with visible growth, globular masses were found upon centrifugation and examination of the sediment. Normal rods were cultivated from the masses in the sediment. In the same year Alture-Werber, Lipschitz, Kashdan, and Rosenblatt (1945)studied the effect of incompletely inhibitory concentrations of penicillin on Escherichia coli. These authors found organisms resembling budding fungi in the urine of patients treated with penicillin. Culturing for molds was negative, but E. coli was isolated on other media and it was concluded that penicillin was responsible for the funguslike appearance of the cells in urine. This assumption was confirmed by in vitro experiments using MacConkey's agar to which was added varying concentrations of penicillin. Morphological changes noted were diphtheroidlike, bipolar cells at 75 units per ml.; unsegmented filaments with myceliallike appearance at 100 units per ml; and at 150 units per ml forms similar to those observed in the urine specimens, designated as zygosporelike bodies. Kojima and Heimbrock (1946) and Fennel (1946) confirmed the findings of Alture-Werber et al. (1945). Both reports indicated that the urine of penicillin-treated patients contained budding funguslike forms, which in one case were identified as B. aerogenes (Aerobacter aerogenes) and in the other as E. coli. Kojima and Heimbrock did not obtain bulbous forms in broth cultures with penicillin, but Fennel found various bizarre types in glucose broth containing various concentrations of penicillin. In all of the foregoing cases, when the organisms showing atypical forms were cultured on media not containing penicillin, only normal rods were found. A short but informative review of the action of penicillin and its effect on bacterial morphology was given by Fisher (1946). Morphological variation may be induced by agents or conditions other than by the use of penicillin. Only a few of the more important aspects of the phe-