{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:20:35Z","timestamp":1792642835932,"version":"4.5.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2017,10,1]],"date-time":"2017-10-01T00:00:00Z","timestamp":1506816000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["DP2OD008459"],"award-info":[{"award-number":["DP2OD008459"]}],"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":["R21AI121805"],"award-info":[{"award-number":["R21AI121805"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["LAMICH16GO"],"award-info":[{"award-number":["LAMICH16GO"]}],"id":[{"id":"10.13039\/100000897","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":[[2017,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            As a growing number of clinical isolates of\n            <jats:named-content content-type=\"genus-species\">Mycobacterium abscessus<\/jats:named-content>\n            are resistant to most antibiotics, new treatment options that are effective against these drug-resistant strains are desperately needed. The majority of the linkages in the cell wall peptidoglycan of\n            <jats:named-content content-type=\"genus-species\">M. abscessus<\/jats:named-content>\n            are synthesized by nonclassical transpeptidases, namely, the\n            <jats:sc>l<\/jats:sc>\n            ,\n            <jats:sc>d<\/jats:sc>\n            -transpeptidases. Emerging evidence suggests that these enzymes represent a new molecular vulnerability in this pathogen. Recent studies have demonstrated that inhibition of these enzymes by the carbapenem class of \u03b2-lactams determines their activity against\n            <jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>\n            . Here, we studied the interactions of \u03b2-lactams with two\n            <jats:sc>l<\/jats:sc>\n            ,\n            <jats:sc>d<\/jats:sc>\n            -transpeptidases in\n            <jats:named-content content-type=\"genus-species\">M. abscessus<\/jats:named-content>\n            , namely, Ldt\n            <jats:sub>Mab1<\/jats:sub>\n            and Ldt\n            <jats:sub>Mab2<\/jats:sub>\n            , and found that both the carbapenem and cephalosporin, but not penicillin, subclasses of \u03b2-lactams inhibit these enzymes. Contrary to the commonly held belief that combination therapy with \u03b2-lactams is redundant, doripenem and cefdinir exhibit synergy against both pansusceptible\n            <jats:named-content content-type=\"genus-species\">M. abscessus<\/jats:named-content>\n            and clinical isolates that are resistant to most antibiotics, which suggests that dual-\u03b2-lactam therapy has potential for the treatment of\n            <jats:named-content content-type=\"genus-species\">M. abscessus<\/jats:named-content>\n            . Finally, we solved the first crystal structure of an\n            <jats:named-content content-type=\"genus-species\">M. abscessus<\/jats:named-content>\n            <jats:sc>l<\/jats:sc>\n            ,\n            <jats:sc>d<\/jats:sc>\n            -transpeptidase, Ldt\n            <jats:sub>Mab2<\/jats:sub>\n            , and using substitutions of critical amino acids in the catalytic site and computational simulations, we describe the key molecular interactions between this enzyme and \u03b2-lactams, which provide an insight into the molecular basis for the relative efficacy of different \u03b2-lactams against\n            <jats:named-content content-type=\"genus-species\">M. abscessus<\/jats:named-content>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.00866-17","type":"journal-article","created":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:35:13Z","timestamp":1501547713000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":80,"title":["Mycobacterium abscessus\n            <scp>l<\/scp>\n            ,\n            <scp>d<\/scp>\n            -Transpeptidases Are Susceptible to Inactivation by Carbapenems and Cephalosporins but Not Penicillins"],"prefix":"10.1128","volume":"61","author":[{"given":"Pankaj","family":"Kumar","sequence":"first","affiliation":[{"name":"Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Taskforce To Study Resistance Emergence and Antimicrobial Development Technology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varsha","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Taskforce To Study Resistance Emergence and Antimicrobial Development Technology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Rog\u00e9rio A.","family":"Silva","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Qu\u00edmica Medicinal e Modelagem Molecular, Instituto de Ci\u00eancias da Sa\u00fade, Universidade Federal do Par\u00e1, Bel\u00e9m, Par\u00e1, Brazil"},{"name":"Laborat\u00f3rio de Planejamento e Desenvolvimento de F\u00e1rmacos, Instituto de Ci\u00eancias Exatas e Naturais, Universidade Federal do Par\u00e1, Bel\u00e9m, Par\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jer\u00f4nimo","family":"Lameira","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Qu\u00edmica Medicinal e Modelagem Molecular, Instituto de Ci\u00eancias da Sa\u00fade, Universidade Federal do Par\u00e1, Bel\u00e9m, Par\u00e1, Brazil"},{"name":"Laborat\u00f3rio de Planejamento e Desenvolvimento de F\u00e1rmacos, Instituto de Ci\u00eancias Exatas e Naturais, Universidade Federal do Par\u00e1, Bel\u00e9m, Par\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe B.","family":"d'Andrea","sequence":"additional","affiliation":[{"name":"Taskforce To Study Resistance Emergence and Antimicrobial Development Technology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Gang","family":"Li","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology, Physiology and Neuroscience, and Medicine, Rutgers University, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan L.","family":"Ginell","sequence":"additional","affiliation":[{"name":"Biosciences Division, Argonne National Laboratory, Argonne, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel S.","family":"Freundlich","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology, Physiology and Neuroscience, and Medicine, Rutgers University, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e1udio Nahum","family":"Alves","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Qu\u00edmica Medicinal e Modelagem Molecular, Instituto de Ci\u00eancias da Sa\u00fade, Universidade Federal do Par\u00e1, Bel\u00e9m, Par\u00e1, Brazil"},{"name":"Laborat\u00f3rio de Planejamento e Desenvolvimento de F\u00e1rmacos, Instituto de Ci\u00eancias Exatas e Naturais, Universidade Federal do Par\u00e1, Bel\u00e9m, Par\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Bailey","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keira A.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2214-0114","authenticated-orcid":false,"given":"Gyanu","family":"Lamichhane","sequence":"additional","affiliation":[{"name":"Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Taskforce To Study Resistance Emergence and Antimicrobial Development Technology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200604-571ST"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200207-678OC"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0b013e328365ab33"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr578"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000104"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb-2016-0234"},{"key":"e_1_3_3_8_2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1128\/9781555819316","volume-title":"Antibiotics: challenges, mechanisms, opportunities","author":"Walsh C","year":"2016","unstructured":"Walsh C WencewiczTA. 2016. Antibiotics: challenges, mechanisms, opportunities, p 37\u201368. ASM Press, Washington, DC."},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00606-10"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00239-08"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2120"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2012.08199.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507384200"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01158-15"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2237"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw022"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb-2016-0208"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01396-13"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1129"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2012.03.015"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444905014356"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1039\/C7MB00110J"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444912048998"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/1469-0691.12405"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks395"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit052"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt410"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw546"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02440-16"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2012.09.016"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.660753"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444906019949"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444906045975"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1107\/S090744490705024X"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444912001308"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904019158"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm051197e"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5CC03202D"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/53.6.880"},{"key":"e_1_3_3_40_2","volume-title":"M24-A2","author":"Desmond E","year":"2011","unstructured":"Desmond E . 2011. Susceptibility testing of mycobacteria, nocardiae and other aerobic actinomycetes. M24-A2. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/0732-8893(93)90087-N"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00866-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00866-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:49:27Z","timestamp":1645476567000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00866-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10]]},"references-count":40,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017,10]]}},"alternative-id":["10.1128\/AAC.00866-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.00866-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10]]},"assertion":[{"value":"2017-04-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-07-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-09-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00866-17"}}