What is it about?

Metallo-β-lactamases (MBLs) that require zinc as essential co-factor can catalyze the hydrolysis of almost all β-lactam antibiotics except for monobactams. MBLs are divided into three subclasses (B1, B2, and B3) based on primary amino acid sequence homology and possess two zinc-binding motifs. Resistance to β-lactam antibiotics through acquired MBL genes is one of the most serious problems in Gram-negative pathogenic bacteria. Thus, we might focus on the significance of the MBL in the environmental Gram-negative pathogens. To find antibiotic resistance gene(s) predating our use of antibiotics through metagenomics, we performed functional screening of a metagenomic library from the deep-seep sediments of Edison seamount (about 10,000 years old).

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Why is it important?

Among 60 antibiotic resistant clones, a single clone with the highest MIC value for ampicillin was selected. The sequence analysis revealed a new metallo-β-lactamase (MBL) gene, designated as blaPNGM-1. PNGM-1 retains a zinc ion-binding motif (H116XH118XD120H121, H196, and H263), conserved in subclass B3 MBLs. The catalytic parameters of purified PNGM-1 and MIC values of β-lactams for E. coli TOP10 harboring blaPNGM-1 gene were assessed. Antimicrobial susceptibility testing indicated reduced susceptibility to penicillins, narrow- and extended-spectrum cephalosporins, and carbapenems. In addition, kinetic analyses revealed that PNGM-1 hydrolyzed almost all β-lactams.

Perspectives

This is the first report of a subclass B3 MBL (PNGM-1) from a metagenomic library of deep-sea Edison seamount sample (about 10,000 years old) that existed prior to the antibiotics era. These results suggest that MBLs are present long before the antibiotic era began, as described in the metagenomic analyses of a member of the TEM group of β-lactamases identified from 30,000-year-old Beringian permafrost sediments.

Professor Sang Hee Lee
Myongji University

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This page is a summary of: PNGM-1, a Novel Subclass B3 Metallo-β-Lactamase from a Deep-Sea Sediment Metagenome, Journal of Global Antimicrobial Resistance, May 2018, Elsevier,
DOI: 10.1016/j.jgar.2018.05.021.
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