Effects of Tetracycline and Spectinomycin on the Tertiary Structure of Ribosomal RNA in the Escherichia coli 30 S Ribosomal Subunit

Noah, James W.; Dolan, Michael; Babin, Patricia; Wollenzien, Paul

doi:10.1074/jbc.274.23.16576

Cited by 44 publications

(42 citation statements)

References 26 publications

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“…The nucleotide substitutions conferring resistance would not directly prohibit formation of these interactions but they may alter the conformation or flexibility of the backbone at positions 965 to 967 to weaken tetracycline binding. Rearrangements in the architecture of helix 31 during tetracycline binding were suggested by the fact that UV induced cross-linking between C1400 and C967 is inhibited completely by tetracycline (18). In terms of the resistance mutations, it is possible that pyrimidinerich sequences in helix 31 loop are not compatible with the tetracycline-induced conformation, leading to weakened tetracycline binding.…”

Section: Discussionmentioning

confidence: 99%

16S rRNA Mutations That Confer Tetracycline Resistance inHelicobacter pyloriDecrease Drug Binding inEscherichia coliRibosomes

Nonaka¹,

Connell

Taylor

2005

J Bacteriol

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Tetracycline resistance in clinical isolates of Helicobacter pylori has been associated with nucleotide substitutions at positions 965 to 967 in the 16S rRNA. We constructed mutants which had different sequences at 965 to 967 in the 16S rRNA gene present on a multicopy plasmid in Escherichia coli strain TA527, in which all seven rrn genes were deleted. The MICs for tetracycline of all mutants having single, double, or triple substitutions at the 965 to 967 region that were previously found in highly resistant H. pylori isolates were higher than that of the mutant exhibiting the wild-type sequence of tetracycline-susceptible H. pylori. The MIC of the mutant with the 965TTC967 triple substitution was 32 times higher than that of the E. coli mutant with the 965AGA967 substitution present in wild-type H. pylori. The ribosomes extracted from the tetracycline-resistant E. coli 965TTC967 variant bound less tetracycline than E. coli with the wild-type H. pylori sequence at this region. The concentration of tetracycline bound to the ribosome was 40% that of the wild type. The results of this study suggest that tetracycline binding to the primary binding site (Tet-1) of the ribosome at positions 965 to 967 is influenced by its sequence patterns, which form the primary binding site for tetracycline.

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Section: Discussionmentioning

confidence: 99%

16S rRNA Mutations That Confer Tetracycline Resistance inHelicobacter pyloriDecrease Drug Binding inEscherichia coliRibosomes

Nonaka¹,

Connell

Taylor

2005

J Bacteriol

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“…However, Schnappinger and Hillen (263) have pointed out that these apparent sites for drug interaction in the ribosome may not necessarily reflect the actual binding site. Indeed, interpretation of the probing studies referred to above is complicated by the observation that binding of tetracycline (which measures approximately 8 by 12 Å ) to the ribosome appears to cause wide-ranging structural change in 16 S rRNA (193). Furthermore, photoincorporation methods are subject to the limitation that upon irradiation, tetracycline photoproducts are generated which may react further with the ribosomes (196).…”

Section: Tet(a) Tet(b) Tet(c) Tet(d) Tet(e) Tet(g) Tet(h) Tet(mentioning

confidence: 99%

Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance

Chopra

Roberts

2001

Microbiol Mol Biol Rev

3,545

2,643

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Tetracyclines were discovered in the 1940s and exhibited activity against a wide range of microorganisms including gram-positive and gram-negative bacteria, chlamydiae, mycoplasmas, rickettsiae, and protozoan parasites. They are inexpensive antibiotics, which have been used extensively in the prophlylaxis and therapy of human and animal infections and also at subtherapeutic levels in animal feed as growth promoters. The first tetracycline-resistant bacterium, Shigella dysenteriae, was isolated in 1953. Tetracycline resistance now occurs in an increasing number of pathogenic, opportunistic, and commensal bacteria. The presence of tetracycline-resistant pathogens limits the use of these agents in treatment of disease. Tetracycline resistance is often due to the acquisition of new genes, which code for energy-dependent efflux of tetracyclines or for a protein that protects bacterial ribosomes from the action of tetracyclines. Many of these genes are associated with mobile plasmids or transposons and can be distinguished from each other using molecular methods including DNA-DNA hybridization with oligonucleotide probes and DNA sequencing. A limited number of bacteria acquire resistance by mutations, which alter the permeability of the outer membrane porins and/or lipopolysaccharides in the outer membrane, change the regulation of innate efflux systems, or alter the 16S rRNA. New tetracycline derivatives are being examined, although their role in treatment is not clear. Changing the use of tetracyclines in human and animal health as well as in food production is needed if we are to continue to use this class of broad-spectrum antimicrobials through the present century

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“…Nucleotide 1054 contacts the A-site tRNA (40) and is very near G1058, the P. acnes tetracycline resistance mutation. Tetracycline binding also disrupts a 16S rRNA cross-link between C967 and C1400 in the E. coli 30S ribosomal subunit (21). The crystal structures of the 30S ribosome-tetracycline complexes show tetracycline interacting primarily with atoms of the phosphodiester backbone of nucleotides in h34 and the loop of h31, the boxed residues in Fig.…”

Section: Vol 184 2002mentioning

confidence: 99%

Mutations in the 16S rRNA Genes ofHelicobacter pyloriMediate Resistance to Tetracycline

Trieber¹,

2002

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Low-cost and rescue treatments for Helicobacter pylori infections involve combinations of several drugs including tetracycline. Resistance to tetracycline has recently emerged in H. pylori. The 16S rRNA gene sequences of two tetracycline-resistant clinical isolates (MIC ‫؍‬ 64 g/ml) were determined and compared to the consensus H. pylori 16S rRNA sequence. One isolate had four nucleotide substitutions, and the other had four substitutions and two deletions. Natural transformation with the 16S rRNA genes from the resistant organisms conferred tetracycline resistance on susceptible strains. 16S rRNA genes containing the individual mutations were constructed and tested for the ability to confer resistance. Only the 16S rRNA gene containing the triple mutation, AGA965-967TTC, was able to confer tetracycline resistance on H. pylori 26695. The MICs of tetracycline for the transformed strains were equivalent to those for the original clinical isolates. The two original isolates were also metronidazole resistant, but this trait was not linked to the tetracycline resistance phenotype. Serial passage of several H. pylori strains on increasing concentrations of tetracycline yielded mutants with only a very modest increase in tetracycline resistance to a MIC of 4 to 8 g/ml. These mutants all had a deletion of G942 in the 16S rRNA genes. The mutations in the 16S rRNA are clearly responsible for tetracycline resistance in H. pylori.

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Effects of Tetracycline and Spectinomycin on the Tertiary Structure of Ribosomal RNA in the Escherichia coli 30 S Ribosomal Subunit

Cited by 44 publications

References 26 publications

16S rRNA Mutations That Confer Tetracycline Resistance inHelicobacter pyloriDecrease Drug Binding inEscherichia coliRibosomes

16S rRNA Mutations That Confer Tetracycline Resistance inHelicobacter pyloriDecrease Drug Binding inEscherichia coliRibosomes

Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance

Mutations in the 16S rRNA Genes ofHelicobacter pyloriMediate Resistance to Tetracycline

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