Inhibition of staphylococcal alpha-toxin. The effect of aromatic polysulphonic acids on the lethal effect of alpha-toxin in mice.

Abstract

1. Certain aromatic polysulphonic acids, previously tested for inhibition of the haemolytic activity of staphylococcal alpha-toxin, together with some additional related compounds, were tested as possible inhibitors of alpha-toxin in mice. 2. Compounds that inhibited the haemolytic activity of alpha-toxin at concentrations of 0.16mm or less [compounds (I), (II), (IV), (V), (VII) and (VIII)] were found to inhibit the lethal effect of alpha-toxin. 3. With the exception of compound (VIII), amounts of 1mg. were required to inhibit 4 LD(50) of toxin when the test compounds were premixed with alpha-toxin before injection; comparable inhibition with 0.3mg. of compound (VIII) was achieved without prolonged premixing. 4. Mixtures of alpha-toxin and compounds (I) and (II) containing an excess of test compound showed markedly diminished inhibitory activities. 5. The ;half-molecule' analogues of group 1 [compounds (III) and (XVIII)] were non-inhibitory. 6. Compounds (I)-(V), when administered separately from alpha-toxin by the same route (intraperitoneal), were active only when injected almost simultaneously with toxin, whereas compounds (VII) and (VIII) were strikingly inhibitory when injected 15min. before or after the toxin. 7. Compound (VIII) failed to inhibit the lethal effect of alpha-toxin when injected by a different route (intravenous).