This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nicoloff, H. Articles by Levy, S. B. Search for Related Content PubMed PubMed Citation Articles by Nicoloff, H. Articles by Levy, S. B.

Role for Tandem Duplication and Lon Protease in AcrAB-TolC- Dependent Multiple Antibiotic Resistance (Mar) in an Escherichia coli Mutant without Mutations in marRAB or acrRAB

Hervé Nicoloff,^1,2 Vincent Perreten,^1,2, Laura M. McMurry,^1,2 and Stuart B. Levy^1,2,3*

Center for Adaptation Genetics and Drug Resistance and the Departments of,¹ Molecular Biology and Microbiology,² Medicine, Tufts University School of Medicine, Boston, Massachusetts 02111³

Received 3 October 2005/ Accepted 5 April 2006

A spontaneous mutant (M113) of Escherichia coli AG100 with an unstable multiple antibiotic resistance (Mar) phenotype was isolated in the presence of tetracycline. Two mutations were found: an insertion in the promoter of lon (lon3::IS186) that occurred first and a subsequent large tandem duplication, dupIS186, bearing the genes acrAB and extending from the lon3::IS186 to another IS186 present 149 kb away from lon. The decreased amount of Lon protease increased the amount of MarA by stabilization of the basal quantities of MarA produced, which in turn increased the amount of multidrug effux pump AcrAB-TolC. However, in a mutant carrying only a lon mutation, the overproduced pump mediated little, if any, increased multidrug resistance, indicating that the Lon protease was required for the function of the pump. This requirement was only partial since resistance was mediated when amounts of AcrAB in a lon mutant were further increased by a second mutation. In M113, amplification of acrAB on the duplication led to increased amounts of AcrAB and multidrug resistance. Spontaneous gene duplication represents a new mechanism for mediating multidrug resistance in E. coli through AcrAB-TolC.

Present address: Institute of Veterinary Bacteriology, University of Berne, Berne, Switzerland.

This article has been cited by other articles:

• Brochet, M., Couve, E., Zouine, M., Poyart, C., Glaser, P. (2008). A Naturally Occurring Gene Amplification Leading to Sulfonamide and Trimethoprim Resistance in Streptococcus agalactiae. J. Bacteriol. 190: 672-680 [Abstract] [Full Text]  
• Nicoloff, H., Perreten, V., Levy, S. B. (2007). Increased Genome Instability in Escherichia coli lon Mutants: Relation to Emergence of Multiple-Antibiotic-Resistant (Mar) Mutants Caused by Insertion Sequence Elements and Large Tandem Genomic Amplifications. Antimicrob. Agents Chemother. 51: 1293-1303 [Abstract] [Full Text]