Studies Pertaining to the Antibacterial Activity of Sulfathiazole and its Methyl Derivative

The Mode of Action of the Sulfonamides

“…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).…”

“…4 The second requisite, that the inhibition be directly related to sulfonamide concentration, has been observed by numerous investigators (27,82,126,154,193); table l gives typical data demonstrating this point. As indicated in some reports (126,205), this proportionality may not, in every case, TABLE 1 Showing the degree of bacteriostasis as observed in blood-agar plates containing different amounts of SA and inoculated with a virulent culture of Streptococcus pyogenes Data from 59 71 0.03 500 52 75 be strictly linear over a large range of concentrations. If, as assumed by some (Section D), sulfonamides affect more loci in the cell as their concentration is increased, one would expect to observe occasionally such discontinuities in relationship.…”

“…Much of the responsibility for this extreme variability in the ratio probably lies in the variable amounts of sulfonamide-antagonists already present in practically all culture media. The other sulfonamides under the same experimental conditions require relatively more PABA to counteract their action (70,75,84,115,205,246,281,284,287). Analysis of the quantitative data shows that the potency of each sulfonamide is directly proportional to its ability to counteract the anti-bacteriostatic action of PABA, in other words, the amount of PABA required to counteract bacteriostasis is approximately the same for the minimal bacteriostatic concentration of each sulfonamide (75,128,281,284).…”

“…Adsorptive processes, unlike interactions between most molecularly dispersed reactants, are often slow to reach equilibrium. This has been tendered as a possible reason for the delay of sulfonamide action when observed (27,205). Cowles (37) reported that he was able to show that it takes time for sulfonamide to enter bacteria and for equilibrium to be reached.…”

“…In mice, PABA has been shown to antagonize SA, SP and ST in hemolytic streptococcal infection (218), to antagonize SA, SP and ST in pneumococcal infection (167), SD in meningococcal infection (218,270), and ST in infection by Klebsiella sp. (205).…”