Abstract
Metallo-β-lactamases (MBLs) are a group of enzymes that can inactivate most commonly used β-lactam-based antibiotics. Among MBLs, New Delhi metallo-β-lactamase-1 (NDM-1) constitutes an urgent threat to public health as evidenced by its success in rapidly disseminating worldwide since its first discovery. Here we report the biochemical and genetic characteristics of a novel MBL, ElBla2, from the marine bacterium Erythrobacter litoralis HTCC 2594. This enzyme has a higher amino acid sequence similarity to NDM-1 (56%) than any previously reported MBL. Enzymatic assays and secondary structure alignment also confirmed the high similarity between these two enzymes. Whole genome comparison of four Erythrobacter species showed that genes located upstream and downstream of elbla2 were highly conserved, which may indicate that elbla2 was lost during evolution. Furthermore, we predicted two prophages, 13 genomic islands and 25 open reading frames related to insertion sequences in the genome of E. litoralis HTCC 2594. However, unlike NDM-1, the chromosome encoded ElBla2 did not locate in or near these mobile genetic elements, indicating that it cannot transfer between strains. Finally, following our phylogenetic analysis, we suggest a reclassification of E. litoralis HTCC 2594 as a novel species: Erythrobacter sp. HTCC 2594.
Highlights
Ever since the first antibiotic, penicillin, was used in the fight against infections caused by bacteria, there have been rising concerns regarding bacterial resistance to antibiotics acquired via the exposure of bacteria to sub-lethal quantities of antibiotics
Expression of ElBla[2] in E. coli BL21 (DE3) conferred increased minimum inhibitory concentrations (MICs) to various β-lactams compared to the control strain (Table 1)
New Delhi metallo-β-lactamase-1 (NDM-1) has been the cause of great concern since it was first reported in 200922
Summary
Ever since the first antibiotic, penicillin, was used in the fight against infections caused by bacteria, there have been rising concerns regarding bacterial resistance to antibiotics acquired via the exposure of bacteria to sub-lethal quantities of antibiotics. Several MBL encoding genes have been found to be associated with mobile genetic elements (MGEs), enabling these genes to spread between species[5,6] Another feature of MBLs is their dependence on metal ions (usually Zn2+) for catalytic activity. Phylogenetic tree analysis showed that ElBla[2] clustered in the same branch as clinical MBLs (NDM-1, VIM-1 and IMP-1) instead of with MBLs from its own genus members[25,26]. All these findings supported continued efforts into a comprehensive study on ElBla[2]. Supported by the phylogenetic analysis, we propose a reclassification of the producer of ElBla[2] as a novel species of genus Erythrobacter
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