Studies on Tie Action of Sulfonamides on the Respira- Tion and Growth of Bacteria' A. Factors Controlling the Inhibition by Sulfonamides of Carboxy-

Studies previously reported on the mode of action of sulfonamides on bacteria showed that the inhibition of respiratory enzymes of the bacteria caused a proportional inhibition of the growth of Streptococcus pyogenes and pneumococcus, type I. This conclusion was based on simultaneous measurements, at various time intervals, of the increase in the number of bacteria (and the mg of bacterial nitrogen) and of the respiration in the presence and absence of 0.04 M sulfanilamide. On the basis of these and other observations, the "inhibition of respiration theory," as the mode of action of sulfonamides, was proposed (Sevag and Shelburne, 1942a, 1942b). This theory, in part, stated that chemotherapeutic agents which possess structural similarity to the whole or part of the coenzyme molecules may specifically combine with the protein component of the respiratory enzymes. This combination may take place as a result of the displacement of coenzymes by the drug, forming an inactive "enzyme analogue," or by a reversible union of the drug with the protein, forming an inactive "drug-proteincoenzyme complex." In this connection it was shown (Sevag, Shelburne, and Mudd, 1942) that sulfonamides exercise inhibitory affinities for bacterial and yeast carboxylases. Sulfathiazole, in comparison with other sulfonamides, being structurally most nearly related to cocarboxylase, exercised markedly greater inhibitory affinity for bacterial carboxylases. The present report represents the results of further studies.