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Journal of Bacteriology, May 1999, p. 2979-2983, Vol. 181, No. 9
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

tRNA Synthetase Mutants of Escherichia coli K-12 Are Resistant to the Gyrase Inhibitor Novobiocin

Jovanovic Milija,dagger Mirjana Lilic,Dagger Radmila Janjusevic, Goran Jovanovic,dagger and Dragutin J. Savic*

Institute of Molecular Genetics and Genetic Engineering, 11001 Belgrade, Yugoslavia

Received 28 September 1998/Accepted 17 February 1999

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 sigma 54) 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.

* Corresponding author. Present address: Department of Microbiology and Immunology, Health Sciences Center, University of Oklahoma, P.O. Box 26901, Oklahoma City, OK 73190. Phone: (405) 271-1202. Fax: (405) 271-3117. E-mail: DRAGUTIN-SAVIC{at}OUHSC.EDU.

dagger Present address: Département de Biochimie Médicale, Centre Médical Universitaire, 1211 Geneva 4, Switzerland.

Dagger Present address: Department of Pathology, New York University, New York, NY.

Journal of Bacteriology, May 1999, p. 2979-2983, Vol. 181, No. 9
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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