SME-type carbapenem-hydrolyzing class A beta-lactamases from geographically diverse Serratia marcescens strains

Three sets of carbapenem-resistant Serratia marcescens isolates have been i dentified in the United States: 1 isolate in Minnesota in 1985 (before appr oval of carbapenems for clinical use), 5 isolates in Los Angeles (Universit y of California at Los Angeles [UCLA]) in 1992, and 19 isolates in Boston f rom 1994 to 1999. All isolates tested produced two p-lactamases, an AmpC-ty pe enzyme with pi values of 8.6 to 9.0 and one with a pi value of approxima tely 9.5. The enzyme with the higher pi in each strain hydrolyzed carbapene ms and was not inhibited by EDTA, similar to the chromosomal class A SME-1 beta -lactamase isolated from the 1982 London strain S. marcescens S6. The genes encoding the carbapenem-hydrolyzing enzymes were cloned in Escherichi a coli and sequenced. The enzyme from the Minnesota isolate had an amino ac id sequence identical to that of SME-1. The isolates from Boston and UCLA p roduced SME-2, an enzyme with a single amino acid change relative to SME-1, a substitution from valine to glutamine at position 207. Purified SME enzy mes from the U.S. isolates had beta -lactam hydrolysis profiles similar to that of the London SME-1 enzyme. Pulsed-field gel electrophoresis analysis revealed that the isolates showed some similarity but differed by at least three genetic events. In conclusion, a family of rare class A carbapenem-hy drolyzing beta -lactamases first described in London has now been identifie d in S. marcescens isolates across the United States.