title: tRNA synthetase mutants of Escherichia coli K-12 are resistant to the gyrase inhibitor novobiocin.
abstract: In previous studies we demonstrated that mutations in the genes cysB, cysE, and cls (nov) affect resistance of Escherichia coli to novobiocin (J. Rakonjac, M. Milic, and D. J. Savic, Mol. Gen. Genet. 228:307-311, 1991; R. Ivanisevic, M. Milic, D. Ajdic, J. Rakonjac, and D. J. Savic, J. Bacteriol. 177:1766-1771, 1995). In this work we expand this list with mutations in rpoN (the gene for RNA polymerase subunit sigma54) and the tRNA synthetase genes alaS, argS, ileS, and leuS. Similarly to resistance to the penicillin antibiotic mecillinam, resistance to novobiocin of tRNA synthetase mutants appears to depend upon the RelA-mediated stringent response. However, at this point the overlapping pathways of mecillinam and novobiocin resistance diverge. Under conditions of stringent response induction, either by the presence of tRNA synthetase mutations or by constitutive production of RelA protein, inactivation of the cls gene diminishes resistance to novobiocin but not to mecillinam.
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, 11001 Belgrade, Yugoslavia.
authors.forename: M
authors.initials: M
authors.lastname: Jovanovic
authors.forename: M
authors.initials: M
authors.lastname: Lilic
authors.forename: R
authors.initials: R
authors.lastname: Janjusevic
authors.forename: G
authors.initials: G
authors.lastname: Jovanovic
authors.forename: D J
authors.initials: DJ
authors.lastname: Savic
authors.forename: J
authors.initials: J
authors.lastname: Milija
mesh_terms: D000412:Alanine-tRNA Ligase / Q000235:genetics; D000560:Amdinocillin / Q000494:pharmacology; D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics*; D001126:Arginine-tRNA Ligase / Q000235:genetics; D004268:DNA-Binding Proteins; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics; D004791:Enzyme Inhibitors; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins; D007533:Isoleucine-tRNA Ligase / Q000235:genetics; D007935:Leucine-tRNA Ligase / Q000235:genetics; D008025:Ligases / Q000378:metabolism; D008565:Membrane Proteins; D009154:Mutation; D009675:Novobiocin / Q000494:pharmacology*; D051877:RNA Polymerase Sigma 54; D012808:Sigma Factor / Q000235:genetics; D059005:Topoisomerase II Inhibitors; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D012808:Sigma Factor; D059005:Topoisomerase II Inhibitors; C497751:rpoN protein, E coli; D009675:Novobiocin; D012321:DNA-Directed RNA Polymerases; D051877:RNA Polymerase Sigma 54; D017855:Transferases (Other Substituted Phosphate Groups); C100091:cardiolipin synthetase; D008025:Ligases; C028812:guanosine 3',5'-polyphosphate synthetases; D000604:Amino Acyl-tRNA Synthetases; D001126:Arginine-tRNA Ligase; D007935:Leucine-tRNA Ligase; D007533:Isoleucine-tRNA Ligase; D000412:Alanine-tRNA Ligase; D000560:Amdinocillin