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dc.contributor.authorShevchuk, Olga
dc.contributor.authorPägelow, Dennis
dc.contributor.authorRasch, Janine
dc.contributor.authorDöhrmann, Simon
dc.contributor.authorGünther, Gabriele
dc.contributor.authorHoppe, Julia
dc.contributor.authorÜnal, Can Murat
dc.contributor.authorBronietzki, Marc
dc.contributor.authorGutierrez, Maximiliano Gabriel
dc.contributor.authorSteinert, Michael
dc.date.accessioned2015-02-26T09:32:52Zen
dc.date.available2015-02-26T09:32:52Zen
dc.date.issued2014-11en
dc.identifier.citationPolyketide synthase (PKS) reduces fusion of Legionella pneumophila-containing vacuoles with lysosomes and contributes to bacterial competitiveness during infection. 2014, 304 (8):1169-81 Int. J. Med. Microbiol.en
dc.identifier.issn1618-0607en
dc.identifier.pmid25218702en
dc.identifier.doi10.1016/j.ijmm.2014.08.010en
dc.identifier.urihttp://hdl.handle.net/10033/345376en
dc.description.abstractL. pneumophila-containing vacuoles (LCVs) exclude endocytic and lysosomal markers in human macrophages and protozoa. We screened a L. pneumophila mini-Tn10 transposon library for mutants, which fail to inhibit the fusion of LCVs with lysosomes by loading of the lysosomal compartment with colloidal iron dextran, mechanical lysis of infected host cells, and magnetic isolation of LCVs that have fused with lysosomes. In silico analysis of the mutated genes, D. discoideum plaque assays and infection assays in protozoa and U937 macrophage-like cells identified well established as well as novel putative L. pneumophila virulence factors. Promising candidates were further analyzed for their co-localization with lysosomes in host cells using fluorescence microscopy. This approach corroborated that the O-methyltransferase, PilY1, TPR-containing protein and polyketide synthase (PKS) of L. pneumophila interfere with lysosomal degradation. Competitive infections in protozoa and macrophages revealed that the identified PKS contributes to the biological fitness of pneumophila strains and may explain their prevalence in the epidemiology of Legionnaires' disease.
dc.language.isoenen
dc.titlePolyketide synthase (PKS) reduces fusion of Legionella pneumophila-containing vacuoles with lysosomes and contributes to bacterial competitiveness during infection.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalInternational journal of medical microbiology : IJMMen
refterms.dateFOA2018-06-13T09:22:58Z
html.description.abstractL. pneumophila-containing vacuoles (LCVs) exclude endocytic and lysosomal markers in human macrophages and protozoa. We screened a L. pneumophila mini-Tn10 transposon library for mutants, which fail to inhibit the fusion of LCVs with lysosomes by loading of the lysosomal compartment with colloidal iron dextran, mechanical lysis of infected host cells, and magnetic isolation of LCVs that have fused with lysosomes. In silico analysis of the mutated genes, D. discoideum plaque assays and infection assays in protozoa and U937 macrophage-like cells identified well established as well as novel putative L. pneumophila virulence factors. Promising candidates were further analyzed for their co-localization with lysosomes in host cells using fluorescence microscopy. This approach corroborated that the O-methyltransferase, PilY1, TPR-containing protein and polyketide synthase (PKS) of L. pneumophila interfere with lysosomal degradation. Competitive infections in protozoa and macrophages revealed that the identified PKS contributes to the biological fitness of pneumophila strains and may explain their prevalence in the epidemiology of Legionnaires' disease.


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