ISSN:
1574-6968
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Biology
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1574-6968.1999.tb08740.x
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