Biochemical properties of staphylococci sensitive and resistant to sulphonamides.

Four staphylococcal substrains resistant to sulphonamides were developed from sensitive parent strains by subcultivation in increasing concentrations of sulphathiazole. As compared with the parent strains, the growth of the resistant strains was 20-200-fold less sensitive to sulphathiazole in a semi-defined medium based on acid hydrolyzed casein than were the parent strains. Inhibition of growth by sulphathiazole was overcome competitively by p-aminobenzoic acid. The inhibition indices of the sulphathiazole-sensitive strains were about 10, and 10@-1000 for the resistant substrains; the change in index was about proportional to the degree of resistance. The sulphathiazole-resistant strains were cross-resistant to other sulphonamides but were not resistant to p-nitrobenzoic acid. Not one of the sensitive or resistant strains was inhibited by aminopterin. No change in the inhibitory effect of sulphathiazole occurred during growth of cultures in its presence, though the drug was partly converted to a second substance (of unknown structure). Resistant and sensitive pairs of strains formed similar amounts of unknown compound, so that it is unlikely that its formation has to do with resistance. Concentrated suspensions of organisms of all strains took up similar amounts of [~~S]-sulphathiazole when incubated in the growth medium. The attachment of the drug to the organisms was weak, but the uptake was not altered by the presence of p-aminobenzoic acid. The rates of aerobic growth and the nutritional requirements for anaerobic growth of sensitive and resistant strains were generally similar. The nutritional requirements for vitamins and amino acids varied among the sensitive strains, but there were only slight differences between resistant and sensitive pairs of strains.