Methylation of 23S rRNA nucleotide G748 by RlmAII methyltransferase renders Streptococcus pneumoniae telithromycin-susceptible.

Methylation of 23S rRNA nucleotide G748 by RlmAII methyltransferase renders Streptococcus pneumoniae telithromycin-susceptible. Antimicrob Agents Chemother. 2013 May 28; Authors: Takaya A, Sato Y, Shoji T, Yamamoto T Abstract Several post-transcriptional modifications of bacterial ribosomal RNAs are important in determining antibiotic resistance or sensitivity. In all gram-positive bacteria, dimethylation of nucleotide at A2058 in domain V of 23S rRNA by a dimethyltransferase Erm(B) results in low susceptibility and resistance to telithromycin (TEL). However, this is insufficient to produce high-level resistance to TEL in Streptococcus pneumoniae. Inactivation of a methyltransferase RlmA(II), which methylates N1 position of a nucleotide at G748 in hairpin 35 of domain II of 23S rRNA, results in increased resistance to TEL of erm(B)-carrying S. pneumoniae. Sixteen TEL-resistant mutants (MICs, 16-32 μg/mL) were isolated from the clinically isolated S. pneumoniae strain showing a low TEL susceptibility (MIC, 2 μg/mL), which resulted in constitutive dimethylation of A2058 by nucleotide differences in the regulatory region of erm(B) mRNA. Primer extension analysis shows the degree of methylation at G748 in all TEL-resistant mutants is significantly reduced by a mutation in the gene encoding RlmA(II) to create a stop codon or change an amino acid residue. Furthermore, RNA footprinting using dimethyl sulfate and the molecular modeling study suggest...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research