The human LL-37 peptide exerts antimicrobial activity against Legionella micdadei interacting with membrane phospholipids |
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| Institution: | 1. Department of Genetics and Microbiology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Sklodowska University, Akademicka 19 St., 20-033, Lublin, Poland;2. Department of Interfacial Phenomena, Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Sklodowska University, Maria Curie-Sklodowska 3 Sq., 20-031 Lublin, Poland;3. Division of Bioanalytical Chemistry, Research Center Borstel, Leibniz Lung Center, Parkallee 1-40, 23845 Borstel, Germany;4. German Center for Infection Research, Thematic Translational Unit Tuberculosis, Partner Site Hamburg-Lübeck-Borstel-Riems, 23845 Borstel, Germany;5. Division of Biophysics, Research Center Borstel, Leibniz Lung Center, Parkallee 10b, 23845 Borstel, Germany;6. Center for Structural Systems Biology (CSSB), Notkestraße 85, Building 15, 22607 Hamburg, Germany;7. Kiel Nano, Surface and Interface Science KiNSIS, Kiel University, Christian-Albrechts-Platz 4, 24118 Kiel, Germany;8. Airway Research Center North, Member of the German Center for Lung Research (DZL), Research Center Borstel, 23845 Borstel, Germany;1. Physics Institute, Universidad Autónoma de San Luis Potosí, Ave. Dr. Manuel Nava #6, San Luis Potosí SLP 78290, Mexico;2. Department of Physiology and Biophysics, Universidad Autónoma de San Luis Potosí School of Medicine, Ave. V. Carranza 2405, San Luis Potosí SLP 78210, Mexico.;1. Institute of Molecular Enzyme Technology, Heinrich Heine University Düsseldorf, Forschungszentrum Jülich GmbH, D-52425 Jülich, Germany;2. Institute of Biochemistry, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany;3. Department of Microbiology and Biotechnology, University of Hamburg, Ohnhorststr. 18, 22609 Hamburg, Germany;4. Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany;5. Centro de Bioinformática y Simulación Molecular (CBSM), Facultad de Ingeniería, Universidad de Talca, 2 Norte 685, CL-3460000 Talca, Chile;6. Synthetic Membrane Systems, Institute of Biochemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany;7. John von Neumann Institute for Computing (NIC), Jülich Supercomputing Centre (JSC), Institute of Biological Information Processing (IBI-7: Structural Biochemistry) & Institute of Bio- and Geosciences (IBG-4: Bioinformatics), Forschungszentrum Jülich GmbH, 52425 Jülich, Germany;8. Institute of Bio- and Geosciences, Plant Sciences (IBG-2) and Agrosphere (IBG-3), Forschungszentrum Jülich GmbH, D-52425 Jülich, Germany;1. National Centre for Biological Sciences-TIFR GKVK Campus, Bellary Road Bangalore 560065 India;2. Faculty of Biosciences, Dept of Neuroscience, Physiology and Pharmacology, University College London, WC1E 6JJ, London;1. Department of Biochemistry, Dokkyo Medical University School of Medicine, Japan;2. Department of Endocrinology and Metabolism, Dokkyo Medical University School of Medicine, Japan;3. Department of Pharmaceutical Sciences, Tohoku University Hospital, Japan;1. Department of Physiology & Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada;2. Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada;3. Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, Manitoba, Canada |
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| Abstract: | Legionella micdadei is responsible for community- or nosocomial-acquired pneumonia as well as the influenza-like illness Pontiac fever. The aim of this study was to investigate the ability of L. micdadei to utilize extracellular choline for phosphatidylcholine (PC) synthesis and its consequences for the phospholipid composition of its membrane system and the interaction with the human LL-37 peptide. Comparative analysis of the PC content using isotopic labeling revealed that in presence of exogenous choline 98% of the total PC was synthesized via the Pcs pathway while the remaining 2% were generated via the PE-methylation (PmtA) pathway. PC species were to a greater extent defined by the Pcs pathway in the outer membrane than in the inner membrane. While no major changes in the bacterial lipid content were observed using 31P NMR, indication for utilization of longer acyl chains and slight increase of PG in response to choline addition was observed by a top-down lipidomics screen. The LL-37 peptide inhibited L. micdadei growth in a dose-dependent manner. Bacteria cultured with exogenous choline were more sensitive to the LL-37 peptide when compared to the standard culture condition. Our biophysical investigations show that the peptide perturbs bacterial-derived phospholipid monolayers and this interaction is dependent on the molar portion of PC. This interaction is responsible for the observed changes in the anti-L. micdadei activity of the LL-37 peptide. |
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