The Mechanism of Resistance to Sulfonamides

Abstract

It has been known for some time that pantothenic acid is effective as a growth vitamin for many bacteria (Williams, 1943). The mechanism involved in the effect of pantothenic acid on growth is, however, not known. The present report deals with a study which indicates that pantothenic acid is involved in the synthesis of tryptophane essential for the multiplication of Staphylococcus aureus. Pantothenate alone or in combination with other vitamins likewise exercises a marked effect upon the resistance of staphylococci to sulfonamides. The relationships between these observations will be described in this paper.It has been observed in this laboratory (see also Gladstone, 1937) that strains of S. aureus can be divided into three classes with respect to their nutritional requirements:1. Nonexacting class. Those which are capable of multiplication in the absence of tryptophane in synthetic media made up of amino acids (table 1, footnote*), also in casein hydrolyzate (table 2, footnote*), each supplemented with vitamins and salts.2. Partialy exacting class. Those capable of multiplication upon the addition of 0.5 per cent glucose to tryptophane-free media.3. Exacting class. Those capable of multiplication only when tryptophane is added to these media, with or without the addition of glucose.The nonexacting and partially exacting strains apparently are able to synthesize tryptophane from amino acids alone and from amino acids and glucose, respectively. Only the partially exacting and exacting strains are considered in this paper. The work of this laboratory has indicated that in staphylococci an inhibition of tryptophane synthesis occurs as one of the results of sulfonamide action Green, 1944a, 1944b). An understanding of the mechanism of tryptophane synthesis by staphylococci is therefore essential from both physiological and chemotherapeutic standpoints, and also in understanding the mechanism of resistance to sulfonamides. RESULTSSource and Variation of Staphylococcus aureus. Through the courtesy of Dr.

The Effect of Several Compounds on the Inhibition of Bacterial Growth by Sulfaguanidine, Sulfamerazine, and Sulfasuxidine

“…Both of these inhibitions are thought to be due to interference by the N' substituted portion of the sulfonamide molecule with a structurally similar part of a coenzyme molecule. Sevag and Green (1944) have shown that sulfonamides interfere with the metabolism of S. aureus by preventing the synthesis or utilization of the essential amino acid, tryptophane. Para-aminobenzoic acid (PABA) reverses the action of almost all of the sulfonamides and is thought to do so because of its structural similarity to the parent molecule, sulfanilamide.…”

The Combined Action of Penicillin and the Sulfonamides in Vitro : The Nature of the Reaction

“…Five of the strains were sulfonamide-susceptible. The sulfonamide-resistant form of each of the strains had been obtained by growing the organisms in increasing concentrations of sulfathiazole (Sevag and Green, 1944).…”

Can Chemotherapy Be Extended to Include the Intracellular Disease Agents?

“…Flavoprotein dehydrogenases (riboflavin phosphoric acid proteins). Sevag and Green (1944) found that growth of certain strains of Staphylococcus aureus in the absence of added glucose is inhibited by sulfathiazole, and that this inhibition is antagonized by riboflavin. Atabrine has been shown by Haas (1944), working with isolated enzyme systems of yeast, to inhibit oxidation mediated by flavoprotein, and this inhibition is antagonized by the coenzyme (cf.…”