Publikationsdatum:
2015-10-15
Beschreibung:
Adenine at position 752 in a loop of helix 35 from positions 745 to 752 in domain II of 23S rRNA is involved in binding to the ribosome of telithromycin (TEL), a member of ketolides. Methylation of guanine at position 748 by the intrinsic methyltransferase RlmA II enhances binding of telithromycin (TEL) to A752 in Streptococcus pneumoniae . We have found that another intrinsic methylation of the adjacent uridine at position 747 enhances G748 methylation by RlmA II , rendering TEL susceptibility. U747 and another nucleotide, U1939, were methylated by the dual-specific methyltransferase RlmCD encoded by SP_1029 in S. pneumoniae . Inactivation of RlmCD reduced N1-methylated level of G748 by RlmA II in vivo , leading to TEL resistance when the nucleotide A2058, located in domain V of 23S rRNA, was dimethylated by the dimethyltransferase Erm(B). In vitro methylation of rRNA showed that RlmA II activity was significantly enhanced by RlmCD-mediated pre-methylation of 23S rRNA. These results suggest that RlmCD-mediated U747 methylation promotes efficient G748 methylation by RlmA II , thereby facilitating TEL binding to the ribosome.
Print ISSN:
0305-1048
Digitale ISSN:
1362-4962
Thema:
Biologie
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