{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:53:43Z","timestamp":1785434023209,"version":"3.56.0"},"reference-count":22,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["EQU202103012588"],"award-info":[{"award-number":["EQU202103012588"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,11,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Mycobacterium abscessus<\/jats:italic>\n (\n Mab<\/jats:italic>\n ) is an\n emerging human pathogen causing severe lung infections in cystic fibrosis\n patients and displays either a smooth (S) or a rough (R) morphotype, the\n latter being associated with a strong inflammatory response. In contrast to\n most other mycobacteria, it possesses only two ESX secretion systems, ESX-3\n and ESX-4. Recent work showed that infection of\n Mab<\/jats:italic>\n S\n lacking the\n eccC3<\/jats:italic>\n -encoding ATPase component of ESX-3 in\n mice was associated with reduced bacterial loads in lungs and no mortality.\n While these studies emphasize the importance of ESX-3 in the virulence of\n Mab<\/jats:italic>\n S, its contribution to the pathogenesis of\n Mab<\/jats:italic>\n R\n in vivo<\/jats:italic>\n remains undefined. Here,\n we exploited an\n Mab<\/jats:italic>\n R mutant lacking\n eccC3<\/jats:italic>\n using the zebrafish model, particularly suited to describe the chronology\n and pathophysiological signs of\n Mab<\/jats:italic>\n R infection. Our\n results clearly show that R \u0394\n eccC3<\/jats:italic>\n was highly\n attenuated in larvae, as evidenced by the enhanced larvae survival, the\n reduced bacterial burden, cord number, and limited proportion of abscesses,\n while functional complementation of\n eccC3<\/jats:italic>\n partially\n restored the phenotypes to wild-type levels. The phenotypes were\n corroborated with whole larvae imaging, showing lower bacterial foci in R\n \u0394\n eccC3<\/jats:italic>\n , as compared to the parental R strain.\n Moreover, infection with R \u0394\n eccC3<\/jats:italic>\n was associated\n with a lower pro-inflammatory response, as showcased by the reduced\n production of\n il1b<\/jats:italic>\n and\n tnfa<\/jats:italic>\n transcripts.\n Together, these findings demonstrate that ESX-3 is a primary driver of\n Mab<\/jats:italic>\n R pathogenicity.\n <\/jats:p>\n \n IMPORTANCE<\/jats:title>\n \n Mycobacterium abscessus<\/jats:italic>\n (\n Mab<\/jats:italic>\n ) is\n currently recognized as an extremely difficult-to-manage pathogen in\n patients with cystic fibrosis. The rough (R) morphotype of\n Mab<\/jats:italic>\n is associated with chronic and more aggressive\n infections in patients than the smooth (S) morphotype. However, the\n mechanisms of pathogenesis of\n Mab<\/jats:italic>\n R remain largely\n unexplored. In this study, we investigated the infection capacity and\n virulence of a\n Mab<\/jats:italic>\n R mutant lacking a functional ESX-3\n secretion system using the zebrafish model. The mutant was severely\n impaired in its ability to replicate in the larvae, and this was\n correlated with a significant increase in larvae survival, highlighting\n the critical role of ESX-3 in\n Mab<\/jats:italic>\n R virulence. Overall,\n this emphasizes ESX-3 as an attractive drug target for future drug\n developments against\n Mab<\/jats:italic>\n R lung diseases.\n <\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/spectrum.01949-25","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T13:04:01Z","timestamp":1759151041000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["EccC3 is essential for pathogenesis of rough\n Mycobacterium abscessus<\/i>\n in zebrafish"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6110-2614","authenticated-orcid":false,"given":"Yara","family":"Tasrini","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/051escj72","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre National de la Recherche Scientifique UMR 9004, Institut de Recherche en Infectiologie de Montpellier (IRIM), Universit\u00e9 de Montpellier","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9026-5333","authenticated-orcid":true,"given":"Wassim","family":"Daher","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/051escj72","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre National de la Recherche Scientifique UMR 9004, Institut de Recherche en Infectiologie de Montpellier (IRIM), Universit\u00e9 de Montpellier","place":["Montpellier, France"]},{"name":"INSERM, IRIM","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6604-4458","authenticated-orcid":true,"given":"Laurent","family":"Kremer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/051escj72","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre National de la Recherche Scientifique UMR 9004, Institut de Recherche en Infectiologie de Montpellier (IRIM), Universit\u00e9 de Montpellier","place":["Montpellier, France"]},{"name":"INSERM, IRIM","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000507"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-020-0331-1"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200604-571ST"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.001054"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1713195115"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01049-21"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens11090953"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-025-07572-4"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.160185"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.28625-0"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12387"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02592-06"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01478-08"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiad007"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02322-10"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1321390111"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13283"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2023.11.011"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005660"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1116238"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02836-23"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005986"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01949-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01949-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T14:08:28Z","timestamp":1762265308000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.01949-25"}},"subtitle":[],"editor":[{"given":"Olivier","family":"Neyrolles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,11,4]]},"references-count":22,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11,4]]}},"alternative-id":["10.1128\/spectrum.01949-25"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.01949-25","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,4]]},"assertion":[{"value":"2025-06-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01949-25"}}