On the action of sulfanilamide

Summary A. According toMellon,Locke andShinn, the bacteriostatic action of sulfanilamide is due to the inactivation of (bacterial) catalase and the resulting accumulation of hydrogen peroxide. The probability of this theory is discussed. B. Catalase activity was studied by means ofPhotobacterium Fischeri, as an oxygen indicator. By adding hydrogen peroxide to the tested cultures of bacteria it has been demonstrated, that: I.Bacterium coli, Photobacterium Fischeri andStreptococcus haemolyticus (strainAronson) contain catalase. II. Sulfanilamide does not inactivate the catalase in blood. III. Sulfanilamide does not inactivate bacterial catalase nor does it affect the production of catalase in the growing culture containing the drug. So we have to conclude that the assumption of catalase inactivation to be the essential factor in sulfanilamide action on bacteria will not lead us to the solution of the problem. First communication:L. K. Wolff andH. W. Julius, Ann. de l'Inst. Pasteur62, 616, 1939.     

On the action of sulfanilamide

Summary Studying the action of sulfanilamide on bacterial nitrogen metabolism, it was shown that: a. Sulfanilamide does not alter the rate of gelatin-hydrolysis by papain or by the proteinase ofB. pyocyaneum andB. prodigiosum. b. Sulfanilamide does not influence the synthesis of aspartic acid from fumaric acid and ammonium chloride by restingB. coli. c. Addition of single amino acids does not counteract sulfanilamide. d. Addition of single amino acids merely accelerates growth slightly; a marked acceleration was obtained only by adding various amino acids simultaneously. e. The addition of such an optimal mixture of amino acids did not exert any influence on the action of sulfanilamide on growth. As the growth acceleration shows that the bacteria are saved an important output of energy in synthesis as a result of the supply of the amino acids, we conclude that sulfanilamide action cannot be due to interference with the synthesis of amino acids from inorganic nitrogen (f.i. NH₂ + pyruvate).Considering these facts, we expect sulfanilamide to pursuit its action on bacterial growth by interfering with protein anabolism, anywhere in the synthesis of protein from amino acids.     

On the action of sulfanilamide

Summary The better activity (in vitro) of various sulfanilamide compounds as compared with sulfanilamide itself is only quantitative,i.e., an equal activity is obtained with lower concentrations. It is shown, that the activity of the studied drugs is so narrowly related to their adsorption in the bacteria (B. coli), that probably the varying activity of the studied compounds is due to differences in adsorbability. For different drugs the adsorbed amount was equal for concentrations with equal activity.The concentration of p. aminobenzoic acid which re-establishes growth — in cultures containing the studied compounds in concentrations of equal activity — was equal in all cases. This fact corroborates the hypothesis, that activity and adsorption are correlated and shows, that the mechanism of action (in vitro) is the same in all cases.Ninth communication: K. C.Winkler, Antonie van Leeuwenhoek9, 115, 1943.     

On the action of sulfanilamide

Summary InE. coli, sulfanilic acid, sulfanilamide, sulfapyridine, sulfapyrimidine and sulfathiazol are antagonized by the same series of non competitive antagonists,viz., methionine, xanthine, serine, thymine and valine. This seems to indicate that the biosynthesis of these substances is successively inhibited by increasing concentrations of these sulfadrugs; the synthesis of methionine being inhibited first, that of valine only by excessive concentrations. Though the absolute concentrations vary with the drug the relative sensitivity of the five enzyme systems are very much the same. This again shows that the intrinsic toxicity of the sulfadrugs is the same.I: Ann. de l'Inst. Pasteur62, 616, 1939. II: Antonie van Leeuwenhoek7, 25, 1941. III: Ibid.7, 77, 1941. IV: Ibid7, 153, 1941. V: Ibid.7, 161, 1941. VI: Ibid.8, 10, 1942. VII: Ibid.8, 86, 1942. VIII: Ibid.8, 139, 1942. IX: Ibid.9, 115, 1943. X: Ibid.10, 1, 1944–1945. XI: Arch. of Biochemistry18. 97, 1948.     

On the action of sulfanilamide

Summary A sulfanilamide activating principle was found to be present in red cells of the horse. This activator substance is active in the rather high dilution of 0.5% haemolysed red cells.The substance or substances are present in the red cells, not in their cell membranes. They seem to be of a protein nature or adsorbed to the protein (haemoglobin).In some media no sulfanilamide action is obtained without the activator. In other media sulfanilamide action, though clearly present, is markedly enhanced. So it must be emphasized, that the substance under discussion is an activator and not a conditio sine qua non for the sulfanilamide action and its characteristics.The substance is activating sulfanilamide against streptococci, staphylococci andB. coli.The substance is not present in human blood or in the red cells of sheep, rabbits or mice.Sixth communication: K. C.Winkler, Antonie van Leeuwenhoek8, 10, 1942.     

On the action of sulfanilamide

Summary Methionine, xanthine and thymine replace para-aminobenzoic acid as a growth factor for the para-aminobenzoic-lessE.coli mutant strain 273.The same substances were able to antagonize non competitively the bacteriostatical activity of 2000 mg/l sulfanilamide completely. It was further shown that the observed differences in sensitivity of the reaction chains leading to methionine, xanthine and thymine are not due to a difference in sensitivity to sulfanilamide but a difference in sensitivity to para-aminobenzoic acid. This seems to indicate that there exists only one reaction which is inhibited by sulfanilamide.XIII: Antonie van Leeuwenhoek15, 136, 1949.     

Studies on the mechanism of action of sulfanilamide on mycelial felts of Rhizoctonia solani

Summary Sulfanilamide induced strong inhibitory effects on the growth, respiration and carbohydrate synthesis by mycelial felts of Rhizoctonia solani. The possible reasons for such inhibitory effects are discussed.The inhibitory effects of sulfanilamide were almost completely alleviated by the inclusion of p-aminobenzoic (PABA) acid in the culture medium of the fungal mats. R. solani normally produces certain amounts of PABA and its growth and metabolism is inhibited in presence of excess of it.