Effects of dihydrostreptomycin on ribosome function in vivo: lack of correlation between changes in ribosome patterns and growth.

In vivo treatment of susceptible Escherichia coli cultures with low concentrations of dihydrostreptomycin leads to a decline in polysomes and a corresponding increase in 70S particles which behave as run-off ribosomes, as well as free 30S and 50S subunits. We have examined the timing and extent of these effects on ribosomes and compared them to the effects of this antibiotic on growth and protein synthesis. We have shown that no changes in ribosome distribution are observed until growth inhibition by dihydrostreptomycin is almost complete. Thus, intracellular dihydrostreptomycin can inhibit growth and net protein synthesis without apparently affecting the ribosome cycle. Since it is known that the antibiotic combines with free 30S subunits, the question is how such combination can bring about the observed inhibition of protein synthesis and growth. We suggest that specific interaction of intracellular antibiotic with proteins of the 30S subunits allows repeated use of the ribosome cycle by such affected particles, but with selective misreading of certain amino acid codons as terminator codons, so that they produce incomplete polypeptide chains. The cumulative effect of such a mechanism would lead to eventual cessation of protein synthesis and growth.