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doi:10.1534/genetics.106.069443
A more recent version of this article appeared on August 1, 2007.
REGULAR RESEARCH PAPERS |
A Fitness Cost Associated with the Antibiotic Resistance Enzyme SME-1 
-lactamase
David C. Marciano 1, Omid Y. Karkouti 1 and Timothy Palzkill 1*
1 Baylor College of Medicine
* To whom correspondence should be addressed. E-mail: timothyp{at}bcm.tmc.edu.
Submitted on December 8, 2006
Revised on January 10, 2007
Accepted on 23 May 2007
The blaTEM-1 
-lactamase gene has become widespread due to the selective pressure of -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 E. 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 â-lactamase. Taken together, these results suggest that fitness costs associated with some -lactamases may limit their dissemination.
Key Words: antibiotic resistance, beta-lactamase, fitness, horizontal gene transfer
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