{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T01:22:28Z","timestamp":1783387348848,"version":"3.54.6"},"reference-count":22,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":147,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005869","name":"University of Fribourg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005869","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The treatment of infections caused by MBL-producing Pseudomonas aeruginosa, including IMP-producers, can be challenging since MBLs confer resistance to most clinically available \u00df-lactams, leaving few viable options. Thiol-containing compounds, such as meso-dimercaptosuccinic acid (DMSA), have been suggested as inhibitors of MBLs, and particularly have been proposed to exert effective activity against IMP-1 enzymes. In this context, we sought to determine the activity of DMSA, in combination with carbapenems or cephalosporins, against diverse MBL and carbapenemase variants, particularly focussing on IMP variants. In recombinant strains producing either IMP-1, IMP-10, or IMP-13, both with and without a functional OprD, synergy was observed with ceftazidime (CAZ), cefepime (FEP), and meropenem. Negligible changes were observed for other MBLs and no effect was observed in stains producing KPC-2. Testing of the CAZ\/DMSA and FEP\/DMSA combinations against clinical IMP-producing P. aeruginosa isolates resulted in fractional inhibitory concentration indexes indicating synergy. Enzymatic assays showed a significantly increased inhibitory activity of DMSA against the IMP variants, compared to the other enzymes tested. These findings highlight a possible role of DMSA or DMSA-like compounds to be developed for the treatment of infections caused by IMP-producing P. aeruginosa.<\/jats:p>","DOI":"10.1093\/femsle\/fnaf052","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T07:32:50Z","timestamp":1748331170000},"source":"Crossref","is-referenced-by-count":1,"title":["Inhibitory activity of meso-dimercaptosuccinic acid against IMP metallo-<i>\u03b2<\/i>-lactamase variants in <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1093","volume":"372","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7335-9001","authenticated-orcid":false,"given":"Jacqueline","family":"Findlay","sequence":"first","affiliation":[{"name":"Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg , 1700 Fribourg ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector","family":"Moreno","sequence":"additional","affiliation":[{"name":"Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg , 1700 Fribourg ,","place":["Switzerland"]},{"name":"Institute of Microbiology, University Hospital Centre and University of Lausanne , 1011 Lausanne ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert","family":"Greub","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, University Hospital Centre and University of Lausanne , 1011 Lausanne ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5455-5576","authenticated-orcid":false,"given":"Christophe","family":"Le\u00a0Terrier","sequence":"additional","affiliation":[{"name":"Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg , 1700 Fribourg ,","place":["Switzerland"]},{"name":"Geneva University Hospitals, Division of Intensive Care , Department of Acute Care Medicine, 1205 Geneva, \u00a0","place":["Switzerland"]},{"name":"Intensive Care and Emergency Medicine, Faculty of Medicine, Department of Anaesthesiology, Pharmacology, \u00a0 University of Geneva, 1211 Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Bouvier","sequence":"additional","affiliation":[{"name":"Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg , 1700 Fribourg ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1343-1622","authenticated-orcid":false,"given":"Patrice","family":"Nordmann","sequence":"additional","affiliation":[{"name":"Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg , 1700 Fribourg ,","place":["Switzerland"]},{"name":"Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg , 1700 Fribourg ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"2025091923030875200_bib1","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1038\/clpt.1989.67","article-title":"Urinary excretion of meso-2,3-dimercaptosuccinic acid in human subjects","volume":"45","author":"Aposhian","year":"1989","journal-title":"Clin Pharmacol Ther"},{"key":"2025091923030875200_bib2","doi-asserted-by":"publisher","first-page":"1060736","DOI":"10.3389\/fgene.2022.1060736","article-title":"Biochemical exploration of \u03b2-lactamase inhibitors","volume":"13","author":"Arer","year":"2023","journal-title":"Front Genet"},{"key":"2025091923030875200_bib3","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1089\/mdr.2024.0104","article-title":"In-vitro activity of dimercaptosuccinic acid in combination with carbapenems against carbapenem-resistant Pseudomonas aeruginosa","volume":"31","author":"Bouvier","year":"2025","journal-title":"Microb Drug Resist"},{"key":"2025091923030875200_bib4","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1093\/qjmed\/hcp114","article-title":"Use of oral dimercaptosuccinic acid (succimer) in adult patients with inorganic lead poisoning","volume":"102","author":"Bradberry","year":"2009","journal-title":"QJM"},{"key":"2025091923030875200_bib5","doi-asserted-by":"publisher","first-page":"3593","DOI":"10.1093\/jac\/dkaa347","article-title":"Dimercaptosuccinic acid in combination with carbapenems against isogenic strains of Escherichia coli producing or not producing a metallo-\u03b2-lactamase in vitro and in murine peritonitis","volume":"75","author":"Cheminet","year":"2020","journal-title":"J Antimicrob Chemother"},{"key":"2025091923030875200_bib6","volume-title":"Performance Standards for Antimicrobial Susceptibility Testing, 33rd Ed. 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