{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T20:48:42Z","timestamp":1773953322649,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DFG","award":["Gu 335\/35-2"],"award-info":[{"award-number":["Gu 335\/35-2"]}]},{"name":"DFG","award":["Gu 335\/38-1"],"award-info":[{"award-number":["Gu 335\/38-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cystic fibrosis (CF) is an autosomal recessive disorder caused by the deficiency of the cystic fibrosis transmembrane conductance regulator (CFTR) and often leads to pulmonary infections caused by various pathogens, including Staphylococcus aureus, Pseudomonas aeruginosa, and nontuberculous mycobacteria, particularly Mycobacterium abscessus. Unfortunately, M. abscessus infections are increasing in prevalence and are associated with the rapid deterioration of CF patients. The treatment options for M. abscessus infections are limited, requiring the urgent need to comprehend infectious pathogenesis and develop new therapeutic interventions targeting affected CF patients. Here, we show that the deficiency of CFTR reduces sphingosine levels in bronchial and alveolar epithelial cells and macrophages from CF mice and humans. Decreased sphingosine contributes to the susceptibility of CF tissues to M. abscessus infection, resulting in a higher incidence of infections in CF mice. Notably, treatment of M. abscessus with sphingosine demonstrated potent bactericidal activity against the pathogen. Most importantly, restoration of sphingosine levels in CF cells, whether human or mouse, and in the lungs of CF mice, provided protection against M. abscessus infections. Our findings demonstrate that pulmonary sphingosine levels are important in controlling M. abscessus infection. These results offer a promising therapeutic avenue for CF patients with pulmonary M. abscessus infections.<\/jats:p>","DOI":"10.3390\/ijms241814004","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T21:34:12Z","timestamp":1694554452000},"page":"14004","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Reduced Sphingosine in Cystic Fibrosis Increases Susceptibility to Mycobacterium abscessus Infections"],"prefix":"10.3390","volume":"24","author":[{"given":"Fabian","family":"Schnitker","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7259-9495","authenticated-orcid":false,"given":"Yongjie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany"},{"name":"West German Heart and Vascular Center, Thoracic Transplantation, Department of Thoracic and Cardiovascular Surgery, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Keitsch","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Soddemann","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5601-2444","authenticated-orcid":false,"given":"Hedda Luise","family":"Verhasselt","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1494-9191","authenticated-orcid":false,"given":"Jan","family":"Kehrmann","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heike","family":"Grassm\u00e9","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6608-8496","authenticated-orcid":false,"given":"Markus","family":"Kamler","sequence":"additional","affiliation":[{"name":"West German Heart and Vascular Center, Thoracic Transplantation, Department of Thoracic and Cardiovascular Surgery, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erich","family":"Gulbins","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany"},{"name":"Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8752-0401","authenticated-orcid":false,"given":"Yuqing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1016\/S0140-6736(16)00576-6","article-title":"Cystic fibrosis","volume":"388","author":"Elborn","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nature04712","article-title":"The ABC protein turned chloride channel whose failure causes cystic fibrosis","volume":"440","author":"Gadsby","year":"2006","journal-title":"Nature"},{"key":"ref_3","first-page":"1662","article-title":"CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine","volume":"10","year":"2019","journal-title":"Front. 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