Re: How does streptomycin actually work?

Hi Joe,

Streptomycin binds to the 30S subunit of the prokaryotic ribosome, interfering with the interaction of the initiator tRNA with the mRNA and the small subunit. In low concentrations, streptomycin induces a misreading of pyrimidines (C and U) in the first and second positions of the mRNA codon (so that a C may be mistaken for a U or a U for a C), and induces misreads of pyrimidnes for A in the first position. This results in consistent errors in protein synthesis that result in slow growth (but not death) of streptomycin susceptible cells. In high concentations, streptomycin completely blocks the initiation of protein synthesis, resulting in cell death.

In particular, ribosomal protein S12 seems to be involved in the mechanism of action of this antibiotic. S12 is not directly bound by streptomycin, but mutations in S12 will confer resistance to streptomycin. Some mutations in the 16S rRNA will also confer resistance to this drug, but others can confer a dependence on streptomycin for translation initiation!

You should be able to find more information about streptomycin in any college-level biochemistry textbook. I recommend Biochemistry by L. Stryer.

You might also be interested in reading one of the original papers about streptomycin resistance :

Funatsu G, Wittmann HG. (1972) Ribosomal proteins. 33. Location of amino-acid replacements in protein S12 isolated from Escherichia coli mutants resistant to streptomycin. Journal of Molecular Biology. 68(3):547-50.