Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2001 Jan;45(1):1-12.
doi: 10.1128/AAC.45.1.1-12.2001.

Macrolide resistance conferred by base substitutions in 23S rRNA

B Vester  1 , S Douthwaite
Affiliations
Review

Macrolide resistance conferred by base substitutions in 23S rRNA

B Vester et al. Antimicrob Agents Chemother. 2001 Jan.
No abstract available

PubMed Disclaimer

Figures

FIG. 1
FIG. 1
Selected clinically important macrolide antibiotics and their derivatives. Two naturally occurring macrolides are shown: erythromycin A, which was the first therapeutic macrolide and possesses a 14-member ring, and tylosin, a 16-member-ring macrolide which has been used extensively in the farming industry both therapeutically and as a growth promoter. Clarithromycin is the 6-methoxy derivative of erythromycin and is presently the drug of choice in H. pylori eradication. The ketolides telithromycin and ABT-773 represent the most recent generation of drugs and are characterized by the 3-ketone group that substitutes the 3-cladinose sugar residue in erythromycin and clarithromycin. Both ketolides have a C-11–C-12 carbamate, which is extended by an alkyl-aryl group in the case of telithromycin. This extension enables telithromycin to make an alternative interaction with domain II of 23S rRNA (see text). Both ketolides are presently undergoing clinical trials, with ABT-773 in the early stage and telithromycin in the final stage of the process.
FIG. 2
FIG. 2
Secondary-structure models of the peptidyl transferase center in domain V of 23S rRNA (A) and hairpin 35 in domain II (B) (60). Nucleotides at which macrolide drugs interact (as defined by chemical footprinting experiments) are indicated (62, 87, 107, 156). The circled nucleotides indicate the positions of mutations that confer macrolide drug resistance in bacterial pathogens and laboratory strains (details and references are given in Table 2). These data are depicted here on the secondary structure of the E. coli rRNA; the rRNA secondary structures of all other organisms are believed to be the same (60, 93). The single-stranded nucleotides involved in macrolide interaction and resistance are conserved in all of the wild-type bacterial rRNAs discussed in this review. However, the identities of the base-paired nucleotides (at positions 754, 2057, and 2611) can vary between different bacteria (see text). Drug abbreviations and classifications are giving in Table 1. Erythromycin and clarithromycin interaction sites on the rRNA are identical.
See this image and copyright information in PMC

References

    1. Aagaard C, Phan H, Trevisanato S, Garrett R A. A spontaneous point mutation in the single 23S rRNA gene of the thermophilic arachaeon Sulfolobus acidocaldarius confers multiple drug resistance. J Bacteriol. 1994;176:7744–7747. - PMC - PubMed
    1. Aagaard C, Rosendahl G, Dam M, Powers T, Douthwaite S. Specific structural probing of plasmid-coded ribosomal RNAs from Escherichia coli. Biochimie. 1991;73:1439–1444. - PubMed
    1. Afseth G, Mallavia L P. Copy number of the 16S rRNA gene in Coxiella burnetii. Eur J Epidemiol. 1997;13:729–731. - PubMed
    1. Agrawal R K, Penczek P, Grassucci R A, Li Y, Leith A, Nierhaus K H, Frank J. Direct visualization of A-, P-, and E-site transfer RNAs in the Escherichia coli ribosome. Science. 1996;271:1000–1002. - PubMed
    1. Andersen L P, Kiilerick S, Pedersen G, Thoreson A C, Jorgensen F, Rath J, Larsen N E, Børup O, Krogfelt K, Scheibel J, Rune S. An analysis of seven different methods to diagnose Helicobacter pylori infections. Scand J Gastroenterol. 1998;33:24–30. - PubMed

Publication types