{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:44:44Z","timestamp":1791531884474,"version":"4.3.4"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Canadian Government | Canadian Institutes of Health Research","award":["PJT183745"],"award-info":[{"award-number":["PJT183745"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,9,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The effectiveness of \u03b2-lactam antibiotics is increasingly threatened by resistant bacteria that harbor hydrolytic \u03b2-lactamase enzymes. Depending on the class of \u03b2-lactamase present, \u03b2-lactam hydrolysis can occur through one of two general molecular mechanisms. Metallo-\u03b2-lactamases (MBLs) require active site Zn\n              <jats:sup>2+<\/jats:sup>\n              ions, whereas serine-\u03b2-lactamases (SBLs) deploy a catalytic serine residue. The result in both cases is drug inactivation via the opening of the \u03b2-lactam warhead of the antibiotic. MBLs confer resistance to most \u03b2-lactams and are non-susceptible to SBL inhibitors, including recently approved diazabicyclooctanes, such as avibactam; consequently, these enzymes represent a growing threat to public health. Aspergillomarasmine A (AMA), a fungal natural product, can rescue the activity of the \u03b2-lactam antibiotic meropenem against MBL-expressing bacterial strains. However, the effectiveness of this \u03b2-lactam\/\u03b2-lactamase inhibitor combination against bacteria producing multiple \u03b2-lactamases remains unknown. We systematically investigated the efficacy of AMA\/meropenem combination therapy with and without avibactam against 10\n              <jats:italic>Escherichia coli<\/jats:italic>\n              and 10\n              <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n              laboratory strains tandemly expressing single MBL and SBL enzymes. Cell-based assays demonstrated that laboratory strains producing NDM-1 and KPC-2 carbapenemases were resistant to the AMA\/meropenem combination but became drug-susceptible upon adding avibactam. We also probed these combinations against 30 clinical isolates expressing multiple \u03b2-lactamases.\n              <jats:italic>E. coli<\/jats:italic>\n              ,\n              <jats:italic>Enterobacter cloacae,<\/jats:italic>\n              and\n              <jats:italic>K. pneumoniae<\/jats:italic>\n              clinical isolates were more susceptible to AMA, avibactam, and meropenem than\n              <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n              and\n              <jats:italic>Acinetobacter baumannii<\/jats:italic>\n              isolates. Overall, the results demonstrate that a triple combination of AMA\/avibactam\/meropenem has potential for empirical treatment of infections caused by multiple \u03b2-lactamase-producing bacteria, especially Enterobacterales.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00272-24","type":"journal-article","created":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T13:01:30Z","timestamp":1723467690000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Efficacy of aspergillomarasmine A\/meropenem combinations with and without avibactam against bacterial strains producing multiple \u03b2-lactamases"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1654-7903","authenticated-orcid":true,"given":"Caitlyn M.","family":"Rotondo","sequence":"first","affiliation":[{"name":"David Braley Centre for Antibiotic Discovery, McMaster University, Hamilton, Ontario, Canada"},{"name":"M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9129-7131","authenticated-orcid":true,"given":"Gerard D.","family":"Wright","sequence":"additional","affiliation":[{"name":"David Braley Centre for Antibiotic Discovery, McMaster University, Hamilton, Ontario, Canada"},{"name":"M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.2889"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3380"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx496"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1911"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.78.082907.145923"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2007.05.021"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.4103\/0974-777X.68531"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/23120053.2015.1074441"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.05041-11"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2012.06796.x"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-019-0159-8"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2017.10.026"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1039\/C8MD00342D"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13445"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01386-19"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.485979"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2016.11.011"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004949"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02622-12"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/249856"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096738"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks121"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02522-13"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10121551"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00036-08"},{"key":"e_1_3_4_27_2","unstructured":"The European Committee on Antimicrobial Susceptibility Testing. 2024. 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