{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:02:25Z","timestamp":1789671745364,"version":"4.0.1"},"reference-count":74,"publisher":"National Academy of Sciences","issue":"38","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["CORLEY23F0"],"award-info":[{"award-number":["CORLEY23F0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["NICK20Y2-SVC"],"award-info":[{"award-number":["NICK20Y2-SVC"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["NICK20Y2"],"award-info":[{"award-number":["NICK20Y2"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["HISERT19R3"],"award-info":[{"award-number":["HISERT19R3"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL167956"],"award-info":[{"award-number":["R01HL167956"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,22]]},"abstract":"<jats:p>\n                    Nontuberculous mycobacteria (NTM) are opportunistic pathogens that cause pulmonary disease (PD) in people with bronchiectasis and other chronic airway diseases. Difficulty treating and eradicating NTM-PD highlights the need for improved understanding of bacterial mechanisms to establish chronic infections. People with the genetic disorder cystic fibrosis (CF) develop bronchiectasis and are the population at highest risk of NTM-PD, caused mainly by\n                    <jats:italic toggle=\"yes\">Mycobacterium avium<\/jats:italic>\n                    or\n                    <jats:italic toggle=\"yes\">Mycobacterium abscessus<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">Mabsc<\/jats:italic>\n                    ). The majority of people with cystic fibrosis (pwCF) and bronchiectasis develop chronic\n                    <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                    airway infections. We hypothesized that antibiotics used to treat\n                    <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    infections could enhance\n                    <jats:italic toggle=\"yes\">Mabsc<\/jats:italic>\n                    persistence in the CF airway. Here, we demonstrate that clinically relevant concentrations of tobramycin, which does not kill\n                    <jats:italic toggle=\"yes\">Mabsc<\/jats:italic>\n                    but is frequently administered to pwCF with chronic\n                    <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    infections, induced\n                    <jats:italic toggle=\"yes\">Mabsc<\/jats:italic>\n                    expression of\n                    <jats:italic toggle=\"yes\">whiB7,<\/jats:italic>\n                    a transcription factor that activates genes associated with resistance to host defenses. Tobramycin promoted\n                    <jats:italic toggle=\"yes\">Mabsc<\/jats:italic>\n                    viability in the presence of hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ), growth in human macrophages, and survival in mice. Deletion of\n                    <jats:italic toggle=\"yes\">whiB7<\/jats:italic>\n                    reduced\n                    <jats:italic toggle=\"yes\">Mabsc<\/jats:italic>\n                    viability in the presence of H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    , decreased\n                    <jats:italic toggle=\"yes\">Mabsc\u2019s<\/jats:italic>\n                    ability to persist in macrophages, and disrupted tobramycin\u2019s ability to enhance\n                    <jats:italic toggle=\"yes\">Mabsc<\/jats:italic>\n                    survival. Transcriptomic data defining the tobramycin-associated WhiB7 regulon revealed differential gene expression of factors that could enhance\n                    <jats:italic toggle=\"yes\">Mabsc<\/jats:italic>\n                    resistance to stress conditions such as those found in the CF lung. Overall, our data indicate that administration of tobramycin to pwCF may have unexpected off-target effects, enhancing\n                    <jats:italic toggle=\"yes\">Mabsc whiB7<\/jats:italic>\n                    expression and promoting\n                    <jats:italic toggle=\"yes\">Mabsc<\/jats:italic>\n                    persistent infection.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2626942123","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:07:04Z","timestamp":1789668424000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Tobramycin enhances\n                    <i>Mycobacterium abscessus<\/i>\n                    fitness through\n                    <i>whiB7<\/i>\n                    induction"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7734-7331","authenticated-orcid":false,"given":"Jodi M.","family":"Corley","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016z2bp30","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, National Jewish Health","place":["Denver"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack H.","family":"Congel","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016z2bp30","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, National Jewish Health","place":["Denver"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey C.","family":"Haist","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016z2bp30","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, National Jewish Health","place":["Denver"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alma E.","family":"Ochoa","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016z2bp30","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, National Jewish Health","place":["Denver"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8097-6059","authenticated-orcid":false,"given":"Kenneth C.","family":"Malcolm","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016z2bp30","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, National Jewish Health","place":["Denver"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Janssen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016z2bp30","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, National Jewish Health","place":["Denver"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry A.","family":"Nick","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016z2bp30","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, National Jewish Health","place":["Denver"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine B.","family":"Hisert","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016z2bp30","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, National Jewish Health","place":["Denver"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2022.06.010"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00036-10"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(23)00324-7"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2016.03.002"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2012.01.006"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thorsurg.2018.09.008"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2018.06.001"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1546751"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00578-2020"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.24913"},{"key":"e_1_3_4_11_2","volume-title":"2020 Annual Data Report","author":"Cystic Fibrosis Foundation Patient Registry","year":"2021","unstructured":"Cystic Fibrosis Foundation Patient Registry, 2020 Annual Data Report (Cystic Fibrosis Foundation, 2021)."},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201207-1160OE"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201404-166OC"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr578"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01879-19"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01132-15"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01353-17"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00119-18"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01347-17"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1011060"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.302588"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.516385"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2023.12.020"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201812-863OT"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/jpids\/piac061"},{"key":"e_1_3_4_26_2","unstructured":"CLSI Fluoroquinolone Breakpoints for Enterobacteriaceae and Pseudomonas aeruginosa. (Clin. Lab. Stand. Inst. 2019)."},{"key":"e_1_3_4_27_2","unstructured":"CLSI AST News Update June 2023: New! CLSI M100-Ed33: Updated Aminoglycoside Breakpoints for Enterobacterales and Pseudomonas aeruginosa. Clin. Lab. Stand. Inst. (2025). https:\/\/clsi.org\/about\/blog\/ast-news-update-june-2023-new-clsi-m100-ed33-updated-aminoglycoside-breakpoints-for-enterobacterales-and-pseudomonas-aeruginosa\/ [Accessed 26 February 2025]."},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc8945"},{"key":"e_1_3_4_29_2","first-page":"33","article-title":"A short introduction to pharmacokinetics","volume":"6","author":"Urso R.","year":"2002","unstructured":"R. Urso, P. Blardi, G. Giorgi, A short introduction to pharmacokinetics. Eur. Rev. Med. Pharmacol. Sci. 6, 33\u201344 (2002).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-020-00685-5"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl328"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.1060"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.30.2.260"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199732020-00002"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ftd.0000195617.69721.a5"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.9.4700-4707.1999"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2015.03.003"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2007.09.006"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008069"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202004-0991OC"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2018-0236MA"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2019-0241TR"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.3389\/ftubr.2026.1781507"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02624-12"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx125"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.1.74-79.1999"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00203-012-0848-4"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-8-114"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2015.11.013"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12387"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01249-13"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01565.x"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14834"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037516"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000988"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01184-21"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.101217.4"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505446102"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2448"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3073"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00625-20"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1021\/es5036255"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900589106"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003120"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.06.049"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2016.12.003"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2015-207360"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa241"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-197612030-00002"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00013-11"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1318"},{"key":"e_1_3_4_72_2","article-title":"Implementation of a mycobacterial CRISPRi platform in Mycobacterium abscessus and demonstration of the essentiality of ftsZMab","volume":"138","author":"Gupta R.","year":"2023","unstructured":"R. Gupta, K. H. Rohde, Implementation of a mycobacterial CRISPRi platform in Mycobacterium abscessus and demonstration of the essentiality of ftsZMab. Tuberc. Edinb. Scotl. 138, 102292 (2023).","journal-title":"Tuberc. Edinb. Scotl."},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241311062"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.207"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2626942123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:07:44Z","timestamp":1789668464000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2626942123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":74,"journal-issue":{"issue":"38","published-print":{"date-parts":[[2026,9,22]]}},"alternative-id":["10.1073\/pnas.2626942123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2626942123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]},"assertion":[{"value":"2026-08-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2626942123"}}