{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:58:02Z","timestamp":1790168282770,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:00:00Z","timestamp":1697500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:00:00Z","timestamp":1697500800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["R01AI132374"],"award-info":[{"award-number":["R01AI132374"]}]},{"name":"HHS | National Institutes of Health","award":["U19AI142731"],"award-info":[{"award-number":["U19AI142731"]}]},{"name":"HHS | National Institutes of Health","award":["U19AI142731"],"award-info":[{"award-number":["U19AI142731"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2023,10,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The clinical utility of rifamycins against non-tuberculous mycobacterial (NTM) disease is limited by intrinsic drug resistance achieved by ADP-ribosyltransferase Arr. By blocking the site of ribosylation, we recently optimized a series of analogs with substantially improved potency against\n                    <jats:italic toggle=\"yes\">Mycobacterium abscessus<\/jats:italic>\n                    . Here, we show that a representative member of this series is significantly more potent than rifabutin against major NTM pathogens expressing Arr, providing a powerful medicinal chemistry approach to expand the antimycobacterial spectrum of rifamycins.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Lung disease caused by a range of different species of non-tuberculous mycobacteria (NTM) is difficult to cure. The rifamycins are very active against\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis,<\/jats:italic>\n                      which causes tuberculosis (TB), but inactive against many NTM species. Previously, we showed that the natural resistance of the NTM\n                      <jats:italic toggle=\"yes\">Mycobacterium abscessus<\/jats:italic>\n                      to rifamycins is due to enzymatic inactivation of the drug by the bacterium. We generated chemically modified versions of rifamycins that prevent inactivation by the bacterium and thus become highly active against\n                      <jats:italic toggle=\"yes\">M. abscessus.<\/jats:italic>\n                      Here, we show that such a chemically modified rifamycin is also highly active against several additional NTM species that harbor the rifamycin inactivating enzyme found in\n                      <jats:italic toggle=\"yes\">M. abscessus<\/jats:italic>\n                      , including\n                      <jats:italic toggle=\"yes\">M. chelonae<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">M. fortuitum<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">M. simiae<\/jats:italic>\n                      . This finding expands the potential therapeutic utility of our novel rifamycins to include several currently difficult-to-cure NTM lung disease pathogens beyond\n                      <jats:italic toggle=\"yes\">M. abscessus.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01900-23","type":"journal-article","created":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T09:03:25Z","timestamp":1694163805000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["Blocking ADP-ribosylation expands the anti-mycobacterial spectrum of rifamycins"],"prefix":"10.1128","volume":"11","author":[{"given":"Uday S.","family":"Ganapathy","sequence":"first","affiliation":[{"name":"Center for Discovery and Innovation, Hackensack Meridian Health","place":["Nutley, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota","place":["Minneapolis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Dartois","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation, Hackensack Meridian Health","place":["Nutley, USA"]},{"name":"Department of Medical Sciences, Hackensack Meridian School of Medicine","place":["Nutley, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney C.","family":"Aldrich","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota","place":["Minneapolis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9604-9452","authenticated-orcid":false,"given":"Thomas","family":"Dick","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation, Hackensack Meridian Health","place":["Nutley, USA"]},{"name":"Department of Medical Sciences, Hackensack Meridian School of Medicine","place":["Nutley, USA"]},{"name":"Department of Microbiology and Immunology, Georgetown University","place":["Washington, DC, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2022.10.013"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201111-2016OC"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201002-0310OC"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa241"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081560"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/147.5.1271"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2009.08.016"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1099\/ijsem.0.003026"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.TNMI7-0045-2017"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0272-5231(02)00016-3"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/529443"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2011.09.019"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1053\/rmed.2002.1444"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2020.105967"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200604-571ST"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix517"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciq237"},{"key":"e_1_3_2_19_2","first-page":"523","article-title":"Rifampicin: a new rifamycin I. bacteriological studies","volume":"17","author":"Arioli V","year":"1967","unstructured":"Arioli V , Pallanza R , Furesz S , Carniti G . 1967. 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