{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:21:46Z","timestamp":1790727706576,"version":"4.1.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T00:00:00Z","timestamp":1517443200000},"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":[[2018,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Carbapenem-resistant\n                    <jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>\n                    are urgent threats to global human health. These organisms produce \u03b2-lactamases with carbapenemase activity, such as the metallo-\u03b2-lactamase NDM-1, which is notable due to its association with mobile genetic elements and the lack of a clinically useful inhibitor. Here we examined the ability of copper to inhibit the activity of NDM-1 and explored the potential of a copper coordination complex as a mechanism to efficiently deliver copper as an adjuvant in clinical therapeutics. An NDM-positive\n                    <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n                    isolate, MS6192, was cultured from the urine of a patient with a urinary tract infection. MS6192 was resistant to antibiotics from multiple classes, including diverse \u03b2-lactams (penicillins, cephalosporins, and carbapenems), aminoglycosides, and fluoroquinolones. In the presence of copper (range, 0 to 2 mM), however, the susceptibility of MS6192 to the carbapenems ertapenem and meropenem increased markedly. In standard checkerboard assays, copper decreased the MICs of ertapenem and meropenem against MS6192 in a dose-dependent manner, suggesting a synergistic mode of action. To examine the inhibitory effect of copper in the absence of other \u03b2-lactamases, the\n                    <jats:italic>bla<\/jats:italic>\n                    <jats:sub>NDM-1<\/jats:sub>\n                    gene from MS6192 was cloned and expressed in a recombinant\n                    <jats:named-content content-type=\"genus-species\">E. coli<\/jats:named-content>\n                    K-12 strain. Analysis of cell extracts prepared from this strain revealed that copper directly inhibited NDM-1 activity, which was confirmed using purified recombinant NDM-1. Finally, delivery of copper at a low concentration of 10 \u03bcM by using the FDA-approved coordination complex copper-pyrithione sensitized MS6192 to ertapenem and meropenem in a synergistic manner. Overall, this work demonstrates the potential use of copper coordination complexes as novel carbapenemase adjuvants.\n                  <\/jats:p>","DOI":"10.1128\/aac.02280-17","type":"journal-article","created":{"date-parts":[[2017,11,13]],"date-time":"2017-11-13T11:41:36Z","timestamp":1510573296000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":46,"title":["Copper Ions and Coordination Complexes as Novel Carbapenem Adjuvants"],"prefix":"10.1128","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9814-6515","authenticated-orcid":false,"given":"Karrera Y.","family":"Djoko","sequence":"first","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia"},{"name":"Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia"},{"name":"Department of Biosciences, Durham University, Durham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud E. S.","family":"Achard","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia"},{"name":"Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3426-1044","authenticated-orcid":false,"given":"Minh-Duy","family":"Phan","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia"},{"name":"Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvin W.","family":"Lo","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, 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Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7203-2640","authenticated-orcid":false,"given":"Steven J.","family":"Hancock","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia"},{"name":"Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate M.","family":"Peters","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia"},{"name":"Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5625-1317","authenticated-orcid":false,"given":"Hanna 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