Open AccessInhibition of IMP‐1 metallo‐β‐lactamase and sensitization of IMP‐1‐producing bacteria by thioester derivatives †
Author(s) -
Hammond Gail G.,
Huber Joann L.,
Greenlee Mark L.,
Laub Joanne B.,
Young Katherine,
Silver Lynn L.,
Balkovec James M.,
Pryor KellyAnn D.,
Wu Joseph K.,
Leiting Barbara,
Pompliano David L.,
Toney Jeffrey H.
Publication year - 1999
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1111/j.1574-6968.1999.tb08740.x
Subject(s) - serratia marcescens , thioester , bacteria , microbiology and biotechnology , escherichia coli , serratia , pseudomonas aeruginosa , klebsiella pneumoniae , enterobacteriaceae , chemistry , enzyme , biochemistry , biology , pseudomonas , genetics , gene
IMP‐1 metallo‐β‐lactamase is a transferable carbapenem‐hydrolyzing enzyme found in some clinical isolates of Pseudomonas aeruginosa , Serratia marcescens and Klebsiella pneumoniae . Bacteria that express IMP‐1 show significantly reduced sensitivity to carbapenems and other β‐lactam antibiotics. A series of thioester derivatives has been shown to competitively inhibit purified IMP‐1. As substrates for IMP‐1, the thioesters yielded thiol hydrolysis products which themselves were reversible competitive inhibitors. The thioesters also increased sensitivity to the carbapenem L‐742,728 in an IMP‐1‐producing laboratory stain of Escherichia coli , but will need further modification to improve their activity in less permeable organisms such as Pseudomonas and Serratia . Nonetheless, the thioester IMP‐1 inhibitors offer an encouraging start to overcoming metallo‐β‐lactamase‐mediated resistance in bacteria.