title: Tiamulin resistance mutations in Escherichia coli.
abstract: Forty "two-step" and 13 "three-step" tiamulin-resistant mutants of Escherichia coli PR11 were isolated and tested for alteration of ribosomal proteins. Mutants with altered ribosomal proteins S10, S19, L3, and L4 were detected. The S19, L3, and L4 mutants were studied in detail. The L3 and L4 mutations did not segregate from the resistance character in transductional crosses and therefore seem to be responsible for the resistance. Extracts of these mutants also exhibited an increased in vitro resistance to tiamulin in the polyuridylic acid and phage R17 RNA-dependent polypeptide synthesis systems, and it was demonstrated that this was a property of the 50S subunit. In the case of the S19 mutant, genetic analysis showed segregation between resistance and the S19 alteration and therefore indicated that mutation of a protein other than S19 was responsible for the resistance phenotype. The isolated ribosomes of the S19, L3, and L4 mutants bound radioactive tiamulin with a considerably reduced strength when compared with those of wild-type cells. The association constants were lower by factors ranging from approximately 20 to 200. When heated in the presence of ammonium chloride, these ribosomes partially regained their avidity for tiamulin.
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D004224:Diterpenes / Q000378:metabolism / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D005798:Genes, Bacterial; D009154:Mutation; D012269:Ribosomal Proteins / Q000235:genetics; D012270:Ribosomes / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D001426:Bacterial Proteins; D004224:Diterpenes; D012269:Ribosomal Proteins; C014224:tiamulin