{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T19:09:27Z","timestamp":1762542567564},"reference-count":73,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            \u03b2-Lactamase production increasingly threatens the effectiveness of \u03b2-lactams, which remain a mainstay of antimicrobial chemotherapy. New activities emerge through both mutation of previously known \u03b2-lactamases and mobilization from environmental reservoirs. The spread of metallo-\u03b2-lactamases (MBLs) represents a particular challenge because of their typically broad-spectrum activities encompassing carbapenems, in addition to other \u03b2-lactam classes. Increasingly, genomic and metagenomic studies have revealed the distribution of putative MBLs in the environment, but in most cases their activity against clinically relevant \u03b2-lactams and, hence, the extent to which they can be considered a resistance reservoir remain uncharacterized. Here we characterize the product of one such gene,\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>Rm3<\/jats:sub>\n            , identified through functional metagenomic sampling of an environment with high levels of biocide exposure.\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>Rm3<\/jats:sub>\n            encodes a subclass B3 MBL that, when expressed in a recombinant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>\n            strain, is exported to the bacterial periplasm and hydrolyzes clinically used penicillins, cephalosporins, and carbapenems with an efficiency limited by high\n            <jats:italic>\n              K\n              <jats:sub>m<\/jats:sub>\n            <\/jats:italic>\n            values. An Rm3 crystal structure reveals the MBL superfamily \u03b1\u03b2\/\u03b2\u03b1 fold, which more closely resembles that in mobilized B3 MBLs (AIM-1 and SMB-1) than other chromosomal enzymes (L1 or FEZ-1). A binuclear zinc site sits in a deep channel that is in part defined by a relatively extended N terminus. Structural comparisons suggest that the steric constraints imposed by the N terminus may limit its affinity for \u03b2-lactams. Sequence comparisons identify Rm3-like MBLs in numerous other environmental samples and species. Our data suggest that Rm3-like enzymes represent a distinct group of B3 MBLs with a wide distribution and can be considered an environmental reservoir of determinants of \u03b2-lactam resistance.\n          <\/jats:p>","DOI":"10.1128\/aac.00750-16","type":"journal-article","created":{"date-parts":[[2016,7,19]],"date-time":"2016-07-19T02:39:00Z","timestamp":1468895940000},"page":"5828-5840","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["Structural and Biochemical Characterization of Rm3, a Subclass B3 Metallo-\u03b2-Lactamase Identified from a Functional Metagenomic Study"],"prefix":"10.1128","volume":"60","author":[{"given":"Ramya","family":"Salimraj","sequence":"first","affiliation":[{"name":"School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihong","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, University of Warwick, Coventry, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Hinchliffe","sequence":"additional","affiliation":[{"name":"School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth M. 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