{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T01:28:34Z","timestamp":1789954114198,"version":"4.0.1"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2010,11,1]],"date-time":"2010-11-01T00:00:00Z","timestamp":1288569600000},"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":[[2010,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In this study, we have evaluated the efficacy of calcium-EDTA (Ca-EDTA) as an inhibitor of bacterial metalloenzymes, such as metallo-\u03b2-lactamase (MBL) and other proteases, in a mouse model of\n            <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n            pneumonia. The simultaneous presence of Ca-EDTA (32 \u03bcg\/ml) reduced the MICs of imipenem (IPM) in all MBL-producing\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            isolates (IMP-1, -2, -7, and -10 and VIM-2) but not non-MBL-producing strains. In the pneumonia model, mice were intranasally infected with MBL-producing\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            and then kept under conditions of hyperoxia to mimic ventilator-associated pneumonia. With both intranasal and subcutaneous administrations, Ca-EDTA significantly potentiated survival benefits of IPM compared to those of IPM alone. Ca-EDTA combination therapy induced a significant reduction of the bacterial burden in the lungs (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05). Furthermore, the inhibition activity of Ca-EDTA against MBL activity was confirmed by using the purified IMP-1 enzyme, which was characterized by a 50% inhibitory concentration (IC\n            <jats:sub>50<\/jats:sub>\n            ) of 55 \u00b1 8.2 \u03bcM. Finally, the protective effects of Ca-EDTA were demonstrated by culture supernatant-induced epithelial cell damage and acute lung injury in mice. These data suggest the therapeutic potential of Ca-EDTA not only by the blocking of MBLs but also by neutralizing tissue-damaging metalloproteases in\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            infections.\n          <\/jats:p>","DOI":"10.1128\/aac.00511-10","type":"journal-article","created":{"date-parts":[[2010,8,17]],"date-time":"2010-08-17T04:29:48Z","timestamp":1282019388000},"page":"4582-4588","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":67,"title":["Efficacy of Calcium-EDTA as an Inhibitor for Metallo-\u03b2-Lactamase in a Mouse Model of\n            <i>Pseudomonas aeruginosa<\/i>\n            Pneumonia"],"prefix":"10.1128","volume":"54","author":[{"given":"Nobumasa","family":"Aoki","sequence":"first","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine, Tokyo 143-8540, Japan"},{"name":"Division of Infection Control and Prevention, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikazu","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine, Tokyo 143-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Tateda","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine, Tokyo 143-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoo","family":"Saga","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine, Tokyo 143-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine, Tokyo 143-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine, Tokyo 143-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Division of Infection Control and Prevention, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinari","family":"Tanabe","sequence":"additional","affiliation":[{"name":"Division of Infection Control and Prevention, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Tsukada","sequence":"additional","affiliation":[{"name":"Division of Infection Control and Prevention, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumitake","family":"Gejyo","sequence":"additional","affiliation":[{"name":"Division of Infection Control and Prevention, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keizo","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine, Tokyo 143-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200405-644ST"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn530"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.58.2.433-438.1990"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.6.2681-2686.1993"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.72.3.2064-2069.2006"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1159\/000140461"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2007.03.007"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.165.7.2105078"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.908967"},{"key":"e_1_3_2_11_2","unstructured":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 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