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Antibacterial activity of ceramide and ceramide analogs against pathogenic Neisseria

Please always quote using this URN: urn:nbn:de:bvb:20-opus-159367
  • Certain fatty acids and sphingoid bases found at mucosal surfaces are known to have antibacterial activity and are thought to play a more direct role in innate immunity against bacterial infections. Herein, we analysed the antibacterial activity of sphingolipids, including the sphingoid base sphingosine as well as short-chain C\(_{6}\) and long-chain C\(_{16}\)-ceramides and azido-functionalized ceramide analogs against pathogenic Neisseriae. Determination of the minimal inhibitory concentration (MIC) and minimal bactericidal concentrationCertain fatty acids and sphingoid bases found at mucosal surfaces are known to have antibacterial activity and are thought to play a more direct role in innate immunity against bacterial infections. Herein, we analysed the antibacterial activity of sphingolipids, including the sphingoid base sphingosine as well as short-chain C\(_{6}\) and long-chain C\(_{16}\)-ceramides and azido-functionalized ceramide analogs against pathogenic Neisseriae. Determination of the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) demonstrated that short-chain ceramides and a ω-azido-functionalized C\(_{6}\)-ceramide were active against Neisseria meningitidis and N. gonorrhoeae, whereas they were inactive against Escherichia coli and Staphylococcus aureus. Kinetic assays showed that killing of N. meningitidis occurred within 2 h with ω–azido-C\(_{6}\)-ceramide at 1 X the MIC. Of note, at a bactericidal concentration, ω–azido-C\(_{6}\)-ceramide had no significant toxic effect on host cells. Moreover, lipid uptake and localization was studied by flow cytometry and confocal laser scanning microscopy (CLSM) and revealed a rapid uptake by bacteria within 5 min. CLSM and super-resolution fluorescence imaging by direct stochastic optical reconstruction microscopy demonstrated homogeneous distribution of ceramide analogs in the bacterial membrane. Taken together, these data demonstrate the potent bactericidal activity of sphingosine and synthetic short-chain ceramide analogs against pathogenic Neisseriae.show moreshow less

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Metadaten
Author: Jérôme Becam, Tim WalterORCiD, Anne Burgert, Jan SchlegelORCiD, Markus Sauer, Jürgen Seibel, Alexandra Schubert-Unkmeir
URN:urn:nbn:de:bvb:20-opus-159367
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Hygiene und Mikrobiologie
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Fakultät für Chemie und Pharmazie / Institut für Organische Chemie
Language:English
Parent Title (English):Scientific Reports
Year of Completion:2017
Volume:7
Pagenumber:17627
Source:Scientific Reports 7:17627 (2017). DOI: 10.1038/s41598-017-18071-w
DOI:https://doi.org/10.1038/s41598-017-18071-w
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 579 Mikroorganismen, Pilze, Algen
Tag:Neisseria; ceramide; ceramide analogs
Release Date:2018/03/28
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2017
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International