Abstract
Metallo-β-lactamases (MBLs) are a family of Zn2+-dependent enzymes that have contributed strongly to the emergence and spread of antibiotic resistance. Novel members as well as variants of existing members of this family are discovered continuously, compounding their threat to global health care. MBLs are divided into three subgroups, i.e. B1, B2 and B3. The recent discovery of an unusual MBL from Serratia proteamaculans (SPR-1) suggests the presence of an additional subgroup, i.e. B4. A database search reveals that SPR-1 has only one homologue from Cronobacter sakazakii, CSA-1.These two MBLs have a unique active site and may employ a mechanism distinct from other MBLs, but reminiscent of some organophosphate-degrading hydrolases.
Highlights
On March 5, 2013, the Centers for Disease Control and Prevention (CDC) published the press release “Action needed to halt spread of deadly bacteria—Data show more inpatients suffering infections from bacteria resistant to all or most antibiotics”
B4 MBLs such as SPR-1 and CSA-1 cluster with the B3 subgroup, are similar to the cluster formed by the B1 and B2 subgroups
It appears that an initial evolutionary separation led to the divergence between the B1/B2 and B3/B4 MBLs, before a second, more recent separation led to the formation of four separate subgroups
Summary
On March 5, 2013, the Centers for Disease Control and Prevention (CDC) published the press release “Action needed to halt spread of deadly bacteria—Data show more inpatients suffering infections from bacteria resistant to all or most antibiotics” (http://www.cdc.gov/media/releases/2013/p0305_deadly_ bacteria.html). A family of bacteria has become increasingly resistant to last-resort antibiotics during the past decade, and more hospitalized OPEN ACCESS. D. Hou et al / American Journal of Molecular Biology 4 (2014) 11-15 the MBLs, for which no clinically useful inhibitors are yet available [1,2]. An example is the MBL NDM-1 that emerged rapidly in 2010; infections by NDM-producing Klebsiella pneumonia have a high risk of being fatal [3]. A potent and clinically useful inhibitor of MBLs is urgently needed
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