{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:58:15Z","timestamp":1790402295631,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T00:00:00Z","timestamp":1500336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["260901"],"award-info":[{"award-number":["260901"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["260872"],"award-info":[{"award-number":["260872"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Agence Nationale de Recherche","award":["ANR-10-EQPX-04-01"],"award-info":[{"award-number":["ANR-10-EQPX-04-01"]}]},{"name":"Agence Nationale de Recherche","award":["ANR-14-CE14-0024"],"award-info":[{"award-number":["ANR-14-CE14-0024"]}]},{"name":"Agence Nationale de Recherche","award":["ANR-14-CE08-0017"],"award-info":[{"award-number":["ANR-14-CE08-0017"]}]},{"name":"Agence Nationale de Recherche","award":["ANR-11-LABX-0015-01"],"award-info":[{"award-number":["ANR-11-LABX-0015-01"]}]},{"DOI":"10.13039\/501100008530","name":"Fonds europ\u00e9en de d\u00e9veloppement r\u00e9gional","doi-asserted-by":"publisher","award":["12001407 (D-AL) Equipex Imaginex BioMed"],"award-info":[{"award-number":["12001407 (D-AL) Equipex Imaginex BioMed"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Region Nord-Pas-de-Calais","award":["12000080"],"award-info":[{"award-number":["12000080"]}]},{"name":"Korea Research Foundation","award":["2012R1A3A2048834"],"award-info":[{"award-number":["2012R1A3A2048834"]}]},{"name":"Korea Research Foundation","award":["2016M3A9B6021209"],"award-info":[{"award-number":["2016M3A9B6021209"]}]},{"name":"Inserm Program ATIP avenir"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans, is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT2 receptors (angiotensin II type 2 receptors; AT2R), and leading to potassium-dependent hyperpolarization. This demonstration paves the way to new nature-inspired analgesic protocols. In this direction, we assess here the hyperpolarizing properties of mycolactone on nociceptive neurons. We developed a dedicated medium-throughput assay based on membrane potential changes, and visualized by confocal microscopy of bis-oxonol-loaded Dorsal Root Ganglion (DRG) neurons. We demonstrate that mycolactone at non-cytotoxic doses triggers the hyperpolarization of DRG neurons through AT2R, with this action being not affected by known ligands of AT2R. This result points towards novel AT2R-dependent signaling pathways in DRG neurons underlying the analgesic effect of mycolactone, with the perspective for the development of new types of nature-inspired analgesics.<\/jats:p>","DOI":"10.3390\/toxins9070227","type":"journal-article","created":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T10:33:14Z","timestamp":1500373994000},"page":"227","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone"],"prefix":"10.3390","volume":"9","author":[{"given":"Ok-Ryul","family":"Song","sequence":"first","affiliation":[{"name":"Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Byul","family":"Kim","sequence":"additional","affiliation":[{"name":"Pain Cognitive Function Research Center, Department of Brain and Cognitive Sciences College of Natural Sciences, Dental Research Institute and Department of Neurobiology and Physiology, School of Dentistry, Seoul National University, Seoul 110-799, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Jouny","sequence":"additional","affiliation":[{"name":"Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Ricard","sequence":"additional","affiliation":[{"name":"Univ. 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Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Lesport","sequence":"additional","affiliation":[{"name":"Laboratories of Excellence, Ion Channel Science and Therapeutics, Institut de G\u00e9nomique Fonctionnelle, 141 rue de la Cardonille, 34094 Montpellier, France"},{"name":"CNRS UMR5203, 141 rue de la Cardonille, 34094 Montpellier, France"},{"name":"INSERM U1191, Univ. Montpellier, 141 rue de la Cardonille, 34094 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8021-0419","authenticated-orcid":false,"given":"Emmanuel","family":"Bourinet","sequence":"additional","affiliation":[{"name":"Laboratories of Excellence, Ion Channel Science and Therapeutics, Institut de G\u00e9nomique Fonctionnelle, 141 rue de la Cardonille, 34094 Montpellier, France"},{"name":"CNRS UMR5203, 141 rue de la Cardonille, 34094 Montpellier, France"},{"name":"INSERM U1191, Univ. 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Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S1473-3099(13)70201-9","article-title":"The urgent need for clinical, diagnostic, and operational research for management of buruli ulcer in africa","volume":"14","author":"Comte","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","unstructured":"World Health Organization (WHO) (2012). Treatment of Mycobacterium ulcerans Disease (Buruli Ulcer), World Health Organization."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1111\/1346-8138.13049","article-title":"Revisiting buruli ulcer","volume":"42","author":"Yotsu","year":"2015","journal-title":"J. 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