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Originally published as Genetics Published Articles Ahead of Print on June 11, 2007.
Genetics, Vol. 176, 2381-2392, August 2007, Copyright © 2007
doi:10.1534/genetics.106.069443
A Fitness Cost Associated With the Antibiotic Resistance Enzyme SME-1 ß-Lactamase
David C. Marciano, Omid Y. Karkouti and Timothy Palzkill1
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030
1 Corresponding author: 1 Baylor Plaza, Houston, TX 77030.
E-mail: timothyp{at}bcm.edu
The blaTEM-1 ß-lactamase gene has become widespread due to the selective pressure of ß-lactam use and its stable maintenance on transferable DNA elements. In contrast, blaSME-1 is rarely isolated and is confined to the chromosome of carbapenem-resistant Serratia marcescens strains. Dissemination of blaSME-1 via transfer to a mobile DNA element could hinder the use of carbapenems. In this study, blaSME-1 was determined to impart a fitness cost upon Escherichia coli in multiple genetic contexts and assays. Genetic screens and designed SME-1 mutants were utilized to identify the source of this fitness cost. These experiments established that the SME-1 protein was required for the fitness cost but also that the enzyme activity of SME-1 was not associated with the fitness cost. The genetic screens suggested that the SME-1 signal sequence was involved in the fitness cost. Consistent with these findings, exchange of the SME-1 signal sequence for the TEM-1 signal sequence alleviated the fitness cost while replacing the TEM-1 signal sequence with the SME-1 signal sequence imparted a fitness cost to TEM-1 ß-lactamase. Taken together, these results suggest that fitness costs associated with some ß-lactamases may limit their dissemination.
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