Abstract
New Delhi metallo-β-lactamase (NDM-1) is a new metallo-β-lactamase (MBL) that has recently emerged as a global threat because it confers bacteria with resistance to almost all clinically used β-lactam antibiotics. To determine the molecular basis of this threat, NDM-1 was purified from Escherichia coli TransB (DE3) carrying cloned blaNDM-1 gene by an anion-exchange chromatography step followed by a gel permeation chromatography step. The purified enzyme was stable even in extremely alkaline buffer (pH 11) and reached its highest activity at a low temperature (15°C), which was different from other MBLs. The 50% inhibition concentration of EDTA against NDM-1 was 412 nM, which showed that NDM-1 was more susceptible to EDTA than other MBLs. The effects of zinc on NDM-1 differed between cephem and carbapenem complexes, but inhibition at high Zn2+ concentration was observed for all of tested β-lactam compounds.
Highlights
New Delhi metallo-b-lactamase (NDM-1) was first reported in a Swedish patient in 2009
A recent study has reported the high resistance of NDM-1positive K. pneumoniae and Escherichia coli strains to all tested antibiotics, except tigecycline and colistin [3]
NDM-1 expression and purification NDM-1 enzyme was purified from a lysate of E. coli TransB
Summary
New Delhi metallo-b-lactamase (NDM-1) was first reported in a Swedish patient in 2009. This patient traveled to New Delhi and acquired a urinary tract infection caused by Klebsiella pneumoniae [1]. Cases of the spread and dissemination of NDM-1-positive K. pneumoniae strains have been reported worldwide since August 2010 [2]. A recent study has reported the high resistance of NDM-1positive K. pneumoniae and Escherichia coli strains to all tested antibiotics, except tigecycline and colistin [3]. NDM-1 belongs to the metallo-b-lactamase (MBL; class B) family, which contains Zn2+ and other divalent cations as cofactors. NDM-1 is more potent in inactivating b-lactam antibiotics than known MBLs. to develop antibiotics that can combat emerging NDM-1-positive pathogens, the catalytic mechanism of NDM-1 needs to be determined
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