Pantothenate studies, II. Evidence from Mutants for interference by salicylate with pantoate synthesis.

Although several workers have observed that the bacteriostatic effect of salicylate can be reversed by pantothenate, there is disagreement about the reaction step affected. Salicylate has been considered to inhibit synthesis of pantoate (Ivanovics, 1942), the conversion of pantoate to pantothenate (Roblin, 1949), and the utilization of pantothenate (Mcllwain, 1943; Work and Work, 1948); Ackeimann and Shive (1948) remained undecided between synthesis and utilization of pantoate. Ivanovics' conclusionl was based on the observation that salicylate in low concentrations inhibited growth of pasntoate-synthesizing organisms but not of pantoate or pantothenate-requiring ones. Furthermore, the concentrations of pantoyl lactonel or pantothenate required for reversal of inhibition of the pantoate synthesizers were the same as for optimal growth of the nonsynthesizers. This comparison, however, involved bacterial species which differed metabolically in more ways than the ability to synthesize pantoate. Moreover, since several amino acids and vitamins have been shown to antagonize salicylate inhibition (IvAnovics, 1942), it is significant that only the pantoate-requiring strains were grown in a complex medium containing peptone. In view of these differences in metabolism and media, absence of salicylate inhibition could not rigorously be ascribed to inability to synthesize pantoate. Roblin seemed justified, therefore, to assign the salicylate block to pantoate utilization on the basis of unpublished observations of Stansly (Roblin, 1951) that salicylate inhibition of Escherichia coli was reversed by pantoate in an apparently competitive manner, though over a narrow range of salicylate concentrations only. Experiments to be described will confirm this observation but will show that the competitive relationship observed is only an apparent one. McIlwain (1943) found that in several pantothenate-requiring species, insensitive to salicylate, mutation to pantoyl taurine resistance induced sensitivity to salicylate without affecting the pantothenate requirement; salicylate inhibition of these mutants could be reversed apparently competitively by pantothenate. This seems to be a special case of a new site of attack for salicylate which is not necessarily relevant to the problem of salicylate inhibition in pantothenate synthesizing strains.