AAC
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hardy, C. D.
Right arrow Articles by Cozzarelli, N. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hardy, C. D.
Right arrow Articles by Cozzarelli, N. R.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 2003, p. 941-947, Vol. 47, No. 3
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.3.941-947.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Alteration of Escherichia coli Topoisomerase IV to Novobiocin Resistance

Christine D. Hardy and Nicholas R. Cozzarelli*

Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3204

Received 2 December 2002/ Accepted 10 December 2002

DNA gyrase and topoisomerase IV (topo IV) are the two essential type II topoisomerases of Escherichia coli. Gyrase is responsible for maintaining negative supercoiling of the bacterial chromosome, whereas topo IV's primary role is in disentangling daughter chromosomes following DNA replication. Coumarins, such as novobiocin, are wide-spectrum antimicrobial agents that primarily interfere with DNA gyrase. In this work we designed an alteration in the ParE subunit of topo IV at a site homologous to that which confers coumarin resistance in gyrase. This parE mutation renders the encoded topo IV approximately 40-fold resistant to inhibition by novobiocin in vitro and imparts a similar resistance to inhibition of topo IV-mediated relaxation of supercoiled DNA in vivo. We conclude that topo IV is a secondary target of novobiocin and that it is very likely to be inhibited by the same mechanism as DNA gyrase.

* Corresponding author. Mailing address: Department of Molecular and Cell Biology, University of California, 401 Barker Hall, Berkeley, CA 94720-3204. Phone: (510) 642-5266. Fax: (510) 643-1079. E-mail: ncozzare{at}socrates.berkeley.edu.

Antimicrobial Agents and Chemotherapy, March 2003, p. 941-947, Vol. 47, No. 3
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.3.941-947.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Clin. Vaccine Immunol. Clin. Microbiol. Rev.
J. Clin. Microbiol. ALL ASM JOURNALS

Copyright © 2003 by the American Society for Microbiology. All rights reserved.