A mutation in the decoding center of Thermus thermophilus 16S rRNA suggests a novel mechanism of streptomycin resistance

Abstract

A spontaneous kanamycin resistance and capreomycin resistance mutation, A1408G, in the decoding center of 16S rRNA, was identified in the extreme thermophile Thermus thermophilus. Unexpectedly, this mutation also confers resistance to streptomycin. We propose a novel mechanism of streptomycin resistance by which A1408G influences conformational changes in 16S rRNA during tRNA selection.

FIG. 1.

Three-dimensional arrangements of A1408, G1491, A1492, and A1493 in the T. thermophilus 30S ribosomal subunit crystal structure with (left) A1492 and A1493 in the flipped-out conformation and in the presence of streptomycin (PDB 1FJG) (left) (3) and with A1492 and A1493 in the tucked-in conformation (PDB 1J5E) (right) (25). A1408 pairs with A1493 in the tucked-in conformation, and the A1408G mutation confers streptomycin resistance. The figure was rendered with PyMol (4).