A new type of inactivation of streptomycin by E. coli.

Previously described cases of streptomycin inactivation by R-factor carrying strains of E. coli have not lead to any measurable decrease in antimicrobial potency in the bulk substrate toward the culture. In these cases each cell inactivates only a few molecules. Out of 1,800 strains of E. coli we have isolated five strains which inactivate streptomycin in large amounts giving a final concentration of the inactivation product of 0.25 mg/ml in 36 hours. Unlike all other streptomycin-resistant strains in investigated these five strains were sensitive to butyl-streptomycylamine, a streptomycin derivative acting in the same way as streptomycin. The crude inactivation product has been isolated. Inorganic phosphate is liberated by treatment with alkaline phosphatase resulting in a streptomycin-like compound without any antimicrobial activity.

Streptomycylamines: difference in activity and mode of action between short-chain and long-chain derivatives.

A homologue series of aliphatic streptomycylamines (SM-amines) have been prepared and tested in vitro (binding to 70S ribosomes) and in vivo (MIC). The short-chain SM-amines act as streptomycin (SM) but are less active than SM. They are inactive towards a SM-resistant Escherichia coli, our strain 042. The long-chain SM-amines are active both towards our sensitive and resistant E. coli, our strains 079 and 042. Their activities are not pH-dependent in contrast to that of SM. However, the higher homologues of the aliphatic amines (C10 Congruent TO C10) are considerably active per se although two to four times less than the corresponding SM-amines. Further, the amines do not compete with the SM-amine for the binding to the ribosomal particles. The binding affinities of these long-chain SM-amines to ribosomes are considerably smaller than that of SM. The binding is however specific as a typical isotope dilution curve can be obtained. We conclude that the long-chain SM-amines have a mode of action different from that of SM.