Antibiotic Resistance in Bacteria Caused by Modified Nucleosides in 23S Ribosomal RNA
Birte Vester and Katherine S. Long
RNA modification enzymes in the manifestation of methyltransferases play a major role in antibiotic resistance in bacteria. The ribosome modifications are almost exclusively methylation of either the 2′‑O‑ribose position or various positions on the bases. A wealth of information on antibiotic resistance caused by methylation of rRNA has been revealed during the last ten years. Modifications at eight 23S rRNA nucleotides (G748, A1067, C1920, A2058, G2470, U2479, A2503 and G2535) on the large ribosomal subunit have so far been revealed as antibiotic resistance determinants. In addition, the absence of intrinsic methylation can also lead to reduced antibiotic susceptibility. Antibiotics typically bind to regions of functional importance and sterically block binding of interacting molecules and/or hinder structural rearrangements needed for ribosome activity. The RNA methyltransferases all act at RNA placed at or near the binding site of the antibiotic to which they confer resistance. The structures of about half of the methyltransferases associated with antibiotic resistance and known to act on 23S rRNA have been determined, but there is at present only limited information on the interaction of the methyltransferases with their RNA targets and the timing of the methylation reactions during ribosome assembly.