Stepwise Sabotage of Susceptibility

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Science  23 Feb 2007:
Vol. 315, Issue 5815, pp. 1055
DOI: 10.1126/science.315.5815.1055b

Streptomycin was the first antibiotic found to target the ribosome; specifically, it works by promoting the misreading of the genetic code during translation. Although resistance to high levels of streptomycin has been assigned to mutations in rrs, the gene encoding 16S ribosomal RNA (rRNA), this mechanism does not account for the observed high prevalence of resistance to low levels of the drug.

Okamoto et al. have found that spontaneous mutations occur rapidly within the bacterially conserved gene gidB, which encodes a 7-methylguanosine methyltransferase specific for 16S rRNA. As a consequence of these mutations, there is a failure to methylate the invariant nucleotide G527, and hence low-level streptomycin resistance is conferred. Even though resistance to most drugs that interact with the ribosome occurs via changes in rRNA sequence, this finding suggests that this mechanism of resistance could be more frequent among bacteria than previously expected. Moreover, it is worrisome that these mutations do not appear to exact any fitness cost and seem to constitute a first step toward the evolution of high-level resistance. — CA

Mol. Microbiol. 63, 1096 (2007).

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