Synthesis of Escherichia coli cell walls in the presence of penicillin.

The mechanism of action of penicillin at the cellular level has been considerably clarified recently. It seems clear that penicillin damages the surface of the bacteria, as first suggested by Cooper (l), and this damage leads to leakage of the cell contents, alteration of the internal environment, and death of the bacteria. On the biochemical level, the evidence is still indirect. Lederberg (a), because of observations of creation of spherical forms of Escherichia coli by penicillin in hypertonic solution, has suggested that synthesis of some component of the cell wall is inhibited preferentially by the antibiotic to such an extent that continued growth of the cytoplasm brings about extrusion of the cell contents as a protoplast (3). Park and Strominger (4) favor this hypothesis since it is consistent with their observation that compounds in part similar in composition to cell wall are released into the medium by Staphylococcus aureus in the presence of penicillin, and these compounds may be precursors of the unfinished walls. An alternative hypothesis has been put forth by Prestidge and Pardee (5). It was suggested that penicillin causes formation of an enzyme that attacks the cell membrane (rather than the cell wall) and that disruption of the membrane results in escape of the cell contents. A further test of this hypothesis has not yet been devised. However, it seemed feasible to test directly the Lederberg hypothesis, and the results of such tests are the subject of the present communication. Measurements were made of cell wall synthesis by E. coli in the presence and the absence of a lethal level of penicillin, and in hypoand hypertonic media. No significant difference in the rates of synthesis of cell wall, relative to the rates of cytoplasmic synthesis, was observed.