{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:27:51Z","timestamp":1785414471843,"version":"3.56.0"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["006496F223"],"award-info":[{"award-number":["006496F223"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R01AI174599,1R01AI155723"],"award-info":[{"award-number":["1R01AI174599,1R01AI155723"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["5R01AI141805"],"award-info":[{"award-number":["5R01AI141805"]}],"id":[{"id":"10.13039\/100000060","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":[[2025,8,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Mycobacterium abscessus<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">Mab<\/jats:italic>\n                      ) poses significant clinical challenges and underscores the urgent need for safer and more effective treatments, including \u03b2-lactams. Among currently available carbapenems, imipenem is widely used to treat\n                      <jats:italic toggle=\"yes\">Mab<\/jats:italic>\n                      infections by combining with other antibiotics. Commercial carbapenems share a common scaffold with C2 modifications, whereas this study focuses on novel carbapenem candidates with C5\u03b1 modifications. We evaluated their antibacterial activity against\n                      <jats:italic toggle=\"yes\">Mab<\/jats:italic>\n                      ATCC 19977 and clinical isolates, as well as their acylation of peptidoglycan target receptors (L,D-transpeptidases [LDTs] and penicillin-binding proteins [PBPs]) and the \u03b2-lactamase enzyme Bla\n                      <jats:sub>Mab<\/jats:sub>\n                      .\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      studies of two C5\u03b1-modified carbapenems, JDB\/NA-1-157 and JDB\/NA-1-208, revealed distinct antibacterial effects. JDB\/NA-1-157 demonstrated potent bacterial killing with low minimum inhibitory concentrations (MICs; 0.125\u20138 mg\/L) and near-complete eradication within 5 days, surpassing the efficacy of the standard-of-care regimen (amikacin + clarithromycin + imipenem). In contrast, JDB\/NA-1-208 exhibited poor bacterial killing, with high MICs (16\u2013256 mg\/L) and limited efficacy in time-kill studies. However, JDB\/NA-1-208 showed synergistic killing when combined with other \u03b2-lactams. Mechanistically, JDB\/NA-1-208 is not a substrate for Bla\n                      <jats:sub>Mab<\/jats:sub>\n                      , while JDB\/NA-1-157 is, albeit with low catalytic efficiency. This is supported by the observation that the addition of avibactam did not enhance synergy with JDB\/NA-1-157. The substantial bacterial killing effect of JDB\/NA-1-157 is attributed to its high binding affinity for PBP-B, PBP-lipo, PonA2, D,D-carboxypeptidase, and LDT1\u20132. These findings highlight the potential of novel C5\u03b1-modified carbapenems, particularly JDB\/NA-1-157, as promising therapeutic candidates for\n                      <jats:italic toggle=\"yes\">Mab<\/jats:italic>\n                      infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00170-25","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T10:46:16Z","timestamp":1750157176000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Novel C5\u03b1-substituted carbapenems enhance\n                    <i>Mycobacterium abscessus<\/i>\n                    killing via selective target binding and reduced hydrolysis by Bla\n                    <sub>Mab<\/sub>"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2472-3264","authenticated-orcid":true,"given":"Eunjeong","family":"Shin","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/051fd9666","id-type":"ROR","asserted-by":"publisher"}],"name":"Louis Stokes Cleveland VA Medical Center, Case Western Reserve University","place":["Cleveland, USA"]},{"id":[{"id":"https:\/\/ror.org\/0377srw41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Case Western Reserve University School of Medicine","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena A.","family":"Taracila","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/051fd9666","id-type":"ROR","asserted-by":"publisher"}],"name":"Louis Stokes Cleveland VA Medical Center, Case Western Reserve University","place":["Cleveland, USA"]},{"id":[{"id":"https:\/\/ror.org\/0377srw41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Case Western Reserve University School of Medicine","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pojun","family":"Quan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042tdr378","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Southern Methodist University","place":["Dallas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Mahbub Kabir","family":"Khan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042tdr378","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Southern Methodist University","place":["Dallas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Cox","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042tdr378","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Southern Methodist University","place":["Dallas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diya","family":"Patel","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042tdr378","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Southern Methodist University","place":["Dallas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3272-7231","authenticated-orcid":true,"given":"Khalid M.","family":"Dousa","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/051fd9666","id-type":"ROR","asserted-by":"publisher"}],"name":"Louis Stokes Cleveland VA Medical Center, Case Western Reserve University","place":["Cleveland, USA"]},{"id":[{"id":"https:\/\/ror.org\/0377srw41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Case Western Reserve University School of Medicine","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aetan","family":"Parmar","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rs6vg23","id-type":"ROR","asserted-by":"publisher"}],"name":"Ohio State University","place":["Columbus, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Nantongo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/051fd9666","id-type":"ROR","asserted-by":"publisher"}],"name":"Louis Stokes Cleveland VA Medical Center, Case Western Reserve University","place":["Cleveland, USA"]},{"id":[{"id":"https:\/\/ror.org\/0377srw41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Nguyen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01j7c0b24","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Division of Infectious Diseases, Rush University Medical Center","place":["Chicago, USA"]},{"name":"Department of Internal Medicine, Division of Infectious Diseases, Rush University Medical Center","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5120-962X","authenticated-orcid":true,"given":"Eric J.","family":"Rubin","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Holland","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health","place":["Bethesda, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0243-131X","authenticated-orcid":true,"given":"Barry N.","family":"Kreiswirth","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04p5zd128","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Discovery and Innovation, Hackensack Meridian Health","place":["Nutley, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1007-791X","authenticated-orcid":false,"given":"John D.","family":"Buynak","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042tdr378","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Southern Methodist University","place":["Dallas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3299-894X","authenticated-orcid":true,"given":"Robert A.","family":"Bonomo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/051fd9666","id-type":"ROR","asserted-by":"publisher"}],"name":"Louis Stokes Cleveland VA Medical Center, Case Western Reserve University","place":["Cleveland, USA"]},{"id":[{"id":"https:\/\/ror.org\/0377srw41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Case Western Reserve University School of Medicine","place":["Cleveland, USA"]},{"id":[{"id":"https:\/\/ror.org\/0377srw41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine","place":["Cleveland, USA"]},{"id":[{"id":"https:\/\/ror.org\/01s2wsy11","id-type":"ROR","asserted-by":"publisher"}],"name":"CWRU-Cleveland VAMC Center for Antibiotic Resistance and Epidemiology (Case VA CARES)","place":["Cleveland, USA"]},{"name":"Department of Biochemistry, CWRU","place":["Cleveland, USA"]},{"name":"Department of Pharmacology, CWRU","place":["Cleveland, USA"]},{"name":"Department of Proteomics and Bioinformatics, CWRU","place":["Cleveland, USA"]},{"id":[{"id":"https:\/\/ror.org\/0377srw41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacology, Case Western Reserve University School of Medicine","place":["Cleveland, USA"]},{"id":[{"id":"https:\/\/ror.org\/0377srw41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Proteomics and Bioinformatics, Case Western Reserve University School of Medicine","place":["Cleveland, USA"]},{"name":"Cleveland Geriatrics Research Education and Clinical Center (GRECC), VANEOHS","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr578"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00798-2019"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks279"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01275-08"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2021.07.035"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2020.06.001"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-197809000-00018"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2011.03991.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00425-19"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01206-17"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt410"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dku510"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02440-16"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz433"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03529-21"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00609-24"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13756-018-0448-4"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01915-18"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02623-18"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00098-20"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.7.2816-2821.2005"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb-2016-0234"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02895-18"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00614-19"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01174-24"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02273"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01956-20"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.00046-22"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00093-22"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.71947"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.1c00185"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14010"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2237"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja308197j"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.66567"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.454"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407606200"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.25"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.3c00683"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa241"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2908.230317"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofad312"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.40993"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00319-24"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02613-18"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00866-17"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00790-22"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2022.106669"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00733-19"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw546"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab535"},{"key":"e_1_3_3_53_2","volume-title":"Document M100-S24Performance standards for antimicrobial susceptibility testing; twenty-fourth informational supplement","author":"CLSI","year":"2014","unstructured":"CLSI. 2014. Document M100-S24. Performance standards for antimicrobial susceptibility testing; twenty-fourth informational supplement. Wayne."},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0134(20010501)43:2<113::aid-prot1023>3.0.co;2-t"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm020503a"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1021\/ci6004299"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00170-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00170-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T21:39:11Z","timestamp":1773178751000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00170-25"}},"subtitle":[],"editor":[{"given":"Sean","family":"Wasserman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,8,6]]},"references-count":55,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8,6]]}},"alternative-id":["10.1128\/aac.00170-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.00170-25","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,6]]},"assertion":[{"value":"2025-01-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00170-25"}}