{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T19:40:48Z","timestamp":1779392448681,"version":"3.53.1"},"reference-count":69,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Spanish Society of Clinical Microbiology and Infectious Diseases"},{"name":"Instituto Salud Carlos III","award":["PI15\/00860"],"award-info":[{"award-number":["PI15\/00860"]}]},{"name":"Spanish Ministry of Economy and Competiveness","award":["SAF2016-75638-R"],"award-info":[{"award-number":["SAF2016-75638-R"]}]},{"name":"Instituto Salud Carlos III","award":["PI14\/00059"],"award-info":[{"award-number":["PI14\/00059"]}]},{"name":"Instituto Salud Carlos III","award":["CP13\/00226"],"award-info":[{"award-number":["CP13\/00226"]}]},{"name":"Instituto Salud Carlos III","award":["RD16\/0016"],"award-info":[{"award-number":["RD16\/0016"]}]},{"DOI":"10.13039\/501100010769","name":"Galician Innovation Agency","doi-asserted-by":"crossref","award":["IN607A 2016\/22"],"award-info":[{"award-number":["IN607A 2016\/22"]}],"id":[{"id":"10.13039\/501100010769","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007496","name":"Biomedical Laboratory Research and Development, VA Office of Research and Development","doi-asserted-by":"crossref","award":["1I01BX001974"],"award-info":[{"award-number":["1I01BX001974"]}],"id":[{"id":"10.13039\/100007496","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI100560"],"award-info":[{"award-number":["R01AI100560"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI063517"],"award-info":[{"award-number":["R01AI063517"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI072219"],"award-info":[{"award-number":["R01AI072219"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The number of infections caused by Gram-negative pathogens carrying carbapenemases is increasing, and the group of carbapenem-hydrolyzing class D \u03b2-lactamases (CHDLs) is especially problematic. Several clinically important CHDLs have been identified in\n            <jats:named-content content-type=\"genus-species\">Acinetobacter baumannii<\/jats:named-content>\n            , including OXA-23, OXA-24\/40, OXA-58, OXA-143, OXA-235, and the chromosomally encoded OXA-51. The selection and dissemination of carbapenem-resistant\n            <jats:named-content content-type=\"genus-species\">A. baumannii<\/jats:named-content>\n            strains constitutes a serious global threat. Carbapenems have been successfully utilized as last-resort antibiotics for the treatment of multidrug-resistant\n            <jats:named-content content-type=\"genus-species\">A. baumannii<\/jats:named-content>\n            infections. However, the spread of OXA carbapenemases is compromising the continued use of these antimicrobials. In response to this clinical issue, it is necessary and urgent to design and develop new specific inhibitors with efficacy against these enzymes. The aim of this work was to characterize the inhibitory activity of LN-1-255 (a 6-alkylidene-2-substituted penicillin sulfone) and compare it to that of two established inhibitors (avibactam and tazobactam) against the most relevant enzymes of each group of class D carbapenemases in\n            <jats:named-content content-type=\"genus-species\">A. baumannii<\/jats:named-content>\n            . The \u03b2-lactamase inhibitor LN-1-255 demonstrated excellent microbiological synergy and inhibition kinetics parameters against all tested CHDLs and a significantly higher activity than tazobactam and avibactam. A combination of carbapenems and LN-1-255 was effective against\n            <jats:named-content content-type=\"genus-species\">A. baumannii<\/jats:named-content>\n            class D carbapenemases. Docking assays confirmed the affinity of LN-1-255 for the active site of these enzymes. LN-1-255 represents a potential new \u03b2-lactamase inhibitor that may have a significant role in eradicating infections caused by\n            <jats:named-content content-type=\"genus-species\">A. baumannii<\/jats:named-content>\n            isolates carrying CHDLs.\n          <\/jats:p>","DOI":"10.1128\/aac.01172-17","type":"journal-article","created":{"date-parts":[[2017,8,15]],"date-time":"2017-08-15T00:40:16Z","timestamp":1502757616000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":35,"title":["Activity of the \u03b2-Lactamase Inhibitor LN-1-255 against Carbapenem-Hydrolyzing Class D \u03b2-Lactamases from Acinetobacter baumannii"],"prefix":"10.1128","volume":"61","author":[{"given":"Juan Carlos","family":"V\u00e1zquez-Ucha","sequence":"first","affiliation":[{"name":"Servicio de Microbiolog\u00eda-Instituto de Investigaci\u00f3n Biom\u00e9dica (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a, A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Maneiro","sequence":"additional","affiliation":[{"name":"Centro Singular de Investigaci\u00f3n en Qu\u00edmica Biol\u00f3xica e Materiais Moleculares (CIQUS) and Departamento de Qu\u00edmica Org\u00e1nica, Universidade de Santiago de Compostela, Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Mart\u00ednez-Guiti\u00e1n","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda-Instituto de Investigaci\u00f3n Biom\u00e9dica (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a, A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Buynak","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Southern Methodist University, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Bethel","sequence":"additional","affiliation":[{"name":"Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Bonomo","sequence":"additional","affiliation":[{"name":"Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA"},{"name":"Departments of Medicine, Pharmacology, Molecular Biology, Microbiology, Biochemistry, Proteomics, and Bioinformatics, the CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germ\u00e1n","family":"Bou","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda-Instituto de Investigaci\u00f3n Biom\u00e9dica (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a, A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Poza","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda-Instituto de Investigaci\u00f3n Biom\u00e9dica (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a, A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepci\u00f3n","family":"Gonz\u00e1lez-Bello","sequence":"additional","affiliation":[{"name":"Centro Singular de Investigaci\u00f3n en Qu\u00edmica Biol\u00f3xica e Materiais Moleculares (CIQUS) and Departamento de Qu\u00edmica Org\u00e1nica, Universidade de Santiago de Compostela, Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Beceiro","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda-Instituto de Investigaci\u00f3n Biom\u00e9dica (INIBIC), Complexo Hospitalario Universitario A Coru\u00f1a, A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00058-07"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1789"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/652152"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajic.2009.12.004"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1950"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-004-4060-9"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/42.1.1"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00762-13"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0924-8579(93)90045-7"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar300327a"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.2.583-588.2001"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.6.1556-1561.2000"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01132-06"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.1.202-208.2005"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00856-09"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02413-12"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01512-08"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00117-13"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00001-07"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki482"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1601.090852"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.5b00090"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-007-0371-8"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2009.09.014"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2009.08.020"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00037-09"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01009-09"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb500703p"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.2174\/092986709789104957"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(99)00325-X"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806833200"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00743-09"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw105"},{"key":"e_1_3_3_35_2","unstructured":"European Committee on Antimicrobial Susceptibility Testing. 2015. Breakpoint tables for interpretation of MICs and zone diameters version 5.0. http:\/\/www.eucast.org\/clinical_breakpoints."},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja104092z"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.3109\/14756366.2012.689296"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.280115"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2013.07.015"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01393-15"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku340"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3040"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0145869"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607557104"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2010.12.042"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12232"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.172"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.485979"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01677-07"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.533562"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.12.4589-4596.2004"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.10.4410-4412.2005"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi051719s"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.04.122"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2010.02.065"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.14.10"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.04.149"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01517-09"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867043364847"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2007.01825.x"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.2013.0127"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-10-279"},{"key":"e_1_3_3_63_2","volume-title":"Performance standards for antimicrobial susceptibility testing: 17th informational supplement M07\u2013A9","author":"Clinical and Laboratory Standards Institute","year":"2012","unstructured":"Clinical and Laboratory Standards Institute. 2012. Performance standards for antimicrobial susceptibility testing: 17th informational supplement M07\u2013A9. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/0732-8893(93)90087-N"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.241442898"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv094"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02625-14"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00089-11"},{"key":"e_1_3_3_69_2","volume-title":"Gaussian 09, revision D.01","author":"Frisch MJ","year":"2009","unstructured":"Frisch MJ TrucksGW SchlegelHB ScuseriaGE RobbMA CheesemanJR ScalmaniG BaroneV MennucciB PeterssonGA NakatsujiH CaricatoM LiX HratchianHP IzmaylovAF BloinoJ ZhengG SonnenbergJL HadaM EharaM ToyotaK FukudaR HasegawaJ IshidaM NakajimaT HondaY KitaoO NakaiH VrevenT MontgomeryJA Jr PeraltaJE OgliaroF BearparkM HeydJJ BrothersE KudinKN StaroverovVN KobayashiR NormandJ RaghavachariK RendellA BurantJC IyengarSS TomasiJ CossiM RegaN MillamJM KleneM KnoxJE CrossJB BakkenV AdamoC JaramilloJ GompertsR StratmannRE YazyevO AustinAJ CammiR PomelliC OchterskiJW MartinRL MorokumaK ZakrzewskiVG VothGA SalvadorP DannenbergJJ DapprichS DanielsAD Farkas\u0308O ForesmanJB OrtizJV CioslowskiJ FoxDJ. 2009. Gaussian 09, revision D.01. Gaussian, Inc., Wallingford, CT."},{"key":"e_1_3_3_70_2","volume-title":"The PyMOL molecular graphics system","author":"DeLano WL","year":"2008","unstructured":"DeLano WL . 2008. The PyMOL molecular graphics system. DeLano Scientific LLC, Palo Alto, CA."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01172-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01172-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:44:48Z","timestamp":1645476288000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01172-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11]]},"references-count":69,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["10.1128\/AAC.01172-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.01172-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11]]},"assertion":[{"value":"2017-06-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-08-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-10-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01172-17"}}