ON THE MODE OF ACTION OF THE SULFONAMIDES

III. PURINES, AMINO ACIDS, PEPTONES AND PANCREAS AS ANTAGONISTS AND POTENTIATORS OF SULFONAMIDE IN E. COLI

¹ From the Departments of Physiology and Pharmacology, of Pediatrics, and of Biochemistry, Duke University School of Medicine, Durham, North Carolina

This work, from one point of view, is an attempt to compose a synthetic medium which will duplicate the antisulfonamide activity of peptones. E. coli was presented with a variety of substances which probably occur in commercial peptones, and by its own response has indicated which of these can affect the sulfonamide-inhibition. The principal results are:

(1) Naturally occurring substances may either antagonize or potentiate the sulfonamides. It is also possible that natural synergists exist. Hitherto all discussion has centered upon the occurrence of antagonists in tissue extracts. Future work will have to decide whether the balance between antagonists and potentiators (and synergists) always favors the antagonists as, for example, now seems to be the case in necrotic processes.

(2) The active substances in commercial peptones may now be divided into two groups. The first group comprises four amino acids, several purines, and possibly p-aminobenzoic acid, and accounts for almost all of the antagonism against sulfanilamide. Against sulfathiazole (and also sulfapyridine and sulfadiazine), however, the first group accounts for almost all of the antagonism only when the inhibition of growth is less than about 65%. At greater inhibitions, a second antagonist P-2, of great power, is active.

(3) The nature of P-2 is unknown. It is water soluble; it is not a known, naturally occurring amino acid or p-aminobenzoic acid. Pancreas seems to be the best source for this agent, though it is neither insulin nor a protein.

(4) The actions of P-2 are such as to suggest that the heterocyclic sulfonamides either act at more than one locus within the bacterium, or what is perhaps less likely, form inactive complexes in the medium. The bearing of these possibilities upon current theories of sulfonamide action is discussed.