Acquired metallo-beta-lactamases and their genetic association with class 1 integrons and ISCR elements in Gram-negative bacteria

Metallo-beta-lactamases (MBLs) can hydrolyze almost all beta-lactam antibiotics and are resistant to clinically available beta-lactamase inhibitors. Numerous types of acquired MBLs have been identified, including IMP, VIM, NDM, SPM, GIM, SIM, DIM, KHM, TMB, FIM and AIM. IMPs and VIMs are the most frequent MBLs and disseminate in members of the family Enterobacteriaceae, Pseudomonas spp. and Acinetobacter spp. Acquired MBL genes are often embedded in integrons, and some are associated with insertion sequence (IS) elements. The class 1 integrons and IS common region (ISCR) elements are usually harbored in transposons and/or plasmids, forming so-called mobile vesicles for horizontal transfer of captured genes between bacteria. Here, we review the MBL superfamily identified in Gram-negative bacteria, with an emphasis on the phylogeny of acquired MBLs and their genetic association with class 1 integrons and IS common region elements.