A fitness cost associated with the antibiotic resistance enzyme SME-1 beta-lactamase.
The bla(TEM-1) beta-lactamase gene has become widespread due to the selective pressure of beta-lactam use and its stable maintenance on transferable DNA elements. In contrast, bla(SME-1) is rarely isolated and is confined to the chromosome of carbapenem-resistant Serratia marcescens strains. Dissemination of bla(SME-1) via transfer to a mobile DNA element could hinder the use of carbapenems. In this study, bla(SME-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 beta-lactamase. Taken together, these results suggest that fitness costs associated with some beta-lactamases may limit their dissemination.
Marciano
David C
DC
Department of Molecular Virology and Microbiology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
Karkouti
Omid Y
OY
Palzkill
Timothy
T
D001483:Base Sequence; D015780:Carbapenems / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D022761:Gene Transfer, Horizontal; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D021382:Protein Sorting Signals / Q000235:genetics; D012706:Serratia marcescens / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics*; D013489:Suppression, Genetic; D001618:beta-Lactamases / Q000235:genetics*
D015780:Carbapenems; D017931:DNA Primers; D004269:DNA, Bacterial; D021382:Protein Sorting Signals; C094219:beta-lactamase Sme-1; D001618:beta-Lactamases