Penicillin Until 1957,
WALTER REED ARMY INST OF RESEARCH WASHINGTON DC
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Penicillin remained for 11 years after its discovery unrecognized as a chemotherapeutic drug. Early studies on its mode of action 1942 revealed that the antibiotic is only bactericidal in growing bacterial cultures. Paradoxically, low concentrations are biologically more active than higher concentrations. Penicillin causes bizarre morphological forms of exposed bacteria. It produces lysis of liquid bacterial cultures unless sucrose is added for osmotic protection. Original hypotheses that penicillin interfered with nucleic acid or protein biosyntheses were erroneous. The discovery of the accumulation of Parks Nucleotides gave rise to the hypothesis that the antibiotic interferes with the biosynthesis of the bacterial cell wall polymer. The binding of radioactive penicillin to bacteria could not be interpreted in terms of the mechanism of action of the antibiotic. In 1957, the prevalent hypothesis explained the bactericidal action of penicillin as a biochemical effect on the biosynthesis of the murein building block of the bacterial cell wall.