Single 23S rRNA mutations at the ribosomal peptidyl transferase centre confer resistance to valnemulin and other antibiotics in Mycobacterium smegmatis by perturbation of the drug binding pocket

  title={Single 23S rRNA mutations at the ribosomal peptidyl transferase centre confer resistance to valnemulin and other antibiotics in Mycobacterium smegmatis by perturbation of the drug binding pocket},
  author={Katherine S Long and Jacob Poehlsgaard and Lykke Haastrup Hansen and Sven N. Hobbie and Erik C B{\"o}ttger and Birte Vester},
  journal={Molecular Microbiology},
Tiamulin and valnemulin target the peptidyl transferase centre (PTC) on the bacterial ribosome. They are used in veterinary medicine to treat infections caused by a variety of bacterial pathogens, including the intestinal spirochetes Brachyspira spp. Mutations in ribosomal protein L3 and 23S rRNA have previously been associated with tiamulin resistance in Brachyspira spp. isolates, but as multiple mutations were isolated together, the roles of the individual mutations are unclear. In this work… 

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The data show a nonpredictable cross-resistance pattern between linezolid, chloramphenicol, clindamycin, and valnemulin, and the significance of mutations at distal nucleotides, either alone or in combination with other mutated nucleotide, in contributing to lineZolid resistance.

Mutations in 23S rRNA gene associated with decreased susceptibility to tiamulin and valnemulin in Mycoplasma gallisepticum.

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Detailed knowledge of the linezolid binding site has facilitated the design of a new generation of oxazolidinones that show improved properties against the known resistance mechanisms.

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A variety of novel and less-characterized mutations associated with S. aureus resistance to oxazolidinones are brought to light and the low resistance potential of torezolid is demonstrated.

Mutation in the L3 Ribosomal Protein Could Be Associated with Risk of Selection of High-Level Linezolid-Resistant Staphylococcus epidermidis Strains.

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Mutations in ribosomal protein L3 and 23S ribosomal RNA at the peptidyl transferase centre are associated with reduced susceptibility to tiamulin in Brachyspira spp. isolates

Chemical footprinting experiments show a reduced binding of tiamulin to ribosomal subunits from mutants with decreased susceptibility to the drug, likely the resistance mechanism for these strains.

Oxazolidinone Resistance Mutations in 23S rRNA ofEscherichia coli Reveal the Central Region of Domain V as the Primary Site of Drug Action

All the characterized resistance mutations were clustered in the vicinity of the central loop of domain V of 23S rRNA, suggesting that this rRNA region plays a major role in the interaction of the drug with the ribosome.

Resistance mutations in 23 S rRNA identify the site of action of the protein synthesis inhibitor linezolid in the ribosomal peptidyl transferase center.

A new representative of oxazolidinone antibiotics, linezolid, was found to be active against bacteria and against the halophilic archaeon Halobacterium halobium, supporting the previous conclusion thatlinezolid inhibits translation at a step different from the catalysis of the peptide bond formation.

The Cfr rRNA Methyltransferase Confers Resistance to Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A Antibiotics

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Linezolid and Tiamulin Cross-Resistance in Staphylococcus aureus Mediated by Point Mutations in the Peptidyl Transferase Center

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It is inferred that the A445G mutation in the gene coding for ribosomal protein L3, which points into the peptidyl transferase cleft, causes tiamulin resistance by alteration of the drug-binding site.

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