Beziehungen zwischen Sulfonamiden und Folinsäure; durch Sulfonamide bedingtes Folinsäurebedürfnis von Bakterien

Abstract

Bacteria are classified after Auhagen (1948) according to their folic acid dependency and their inhibition by sulf onamides into 3 groups: Group A requires no folic acid in its substrate and its growth is suppressed by sulfonamides; this suppression of growth is not nullified by addition of folic acid. Group B likewise uses no folic acid and is suppressed by sulfonamides, but the suppression is neutralized by addition of small amts. of folic acid. Group C requires folic acid and is not suppressed by sulfonamides. Representatives of group A are Gram-negative, those of group B and C are Gram-positive. Sulfonamide inhibition of growth of representatives of group A is competitively neutralized by the addition of p-aminobenzoic acid, but neutralization of sulfonamide inhibition in members of group B is accomplished by very small quantities of folic acid. This non-competitive antagonism is explained on the basis that sulfonamides prevent synthesis of folic acid but not its function. It is further shown that bacteria of group B after sulfonamide adaptation are modified in the direction of the representatives of group C, so that they also require folic acid in their media. This result was accomplished by 2-3 passages through a sulfathiazole and folic acid-containing medium. This folic acid dependency, however, is again lost after 2 passages through a sulfathiazole -free but folic acid-containing medium. This reversible transformation is explained on the basis that during passages the protein-bound p-aminobenzoic acid was exchanged according to the law of mass action for sulfathiazole, and synthesis of folic acid from p-aminobenzoic acid was interfered with. Then passages through sulfathiazole-free medium gradually facilitated independent synthesis of folic acid and thereby enabled growth in a folic acid free substrate.