Mode of Action of Sulphonamides in Vitro

The Mode of Action of the Sulfonamides

“…Woods and Fildes (284,285) first demonstrated PABA antagonism of sulfonamide inhibition of bacterial growth. This antagonism to the action of all the sulfonamides on bacteria in vitro has been confirmed by many workers under very wide experimental conditions (75,83,91,179,227,286); in fact, to date no single report denies the counteraction of sulfonamide action on bacteria by PABA. PABA antagonism is also manifest in vivo.…”

“…The relationship existing between sulfonamide and the antagonist PABA is a competitive one as has been shown by Wyss (286) and by Wood (281) using E. coli. In the presence of PABA the growth-stimulating concentration of SA is increased (136), and, over a wide range of concentrations, the ratio of sulfonamide to the amount of PABA required for antagonism is more or less constant (84,173,205,227,269,281,284,287); these two observations are to be expected from the mass law relationship and, therefore, they offer further support for such a relationship. It has been found that one mole of PABA will counteract approximately 1,000 to 26,000 or more moles of SA (43,70,75,163,226,281,284,287).…”

“…This is to be expected from the law of mass action (124). As has been pointed out by several investigators (173,227,281), such a large ratio as one mole of PABA to 1,000-26,000 moles of SA does not rule out competitive inhibition between the sulfonamide and PABA; it could be that the relative affinities are widely separated. These high molar ratios, however, are figured from data obtained in a pH range where practically all the SA activity is a function of the SA-ion, and if the ratio of SA-ions to PABA is used to represent the actual competitors in the reaction, values much nearer unity are obtained (75).…”

THE OXIDATION OF p-AMINOBENZOIC ACID AND ANTHRANILIC ACID BY SPECIFICALLY ADAPTED ENZYMES OF A SOIL BACILLUS

“…In the case of each of these bacterial species, however, the test is not entirely specific. According to the studies of Rubbo and Gillespie (16) there are a number of substances closely related to PABA which show appreciable activity as growth factors for this Clostridium, and p-aminophenylacetic acid in even more active than PABA itself. Anthranilic acid is 100,000 times less active than PABA but, in a concentration of 2 gamma per cc., it too stimulates the growth of the Clostridium.…”

“…In the case of Cl. acetobutylicum, p-aminophenylacetic acid has been" shown to be ten times more active than PABA itself as a growth factor (16). There are a number of other compounds chemically related to PABA which also show definite activity in stimulating the growth of each of the microorganisms mentioned.…”