Polyketide synthase (PKS) reduces fusion of Legionella pneumophila-containing vacuoles with lysosomes and contributes to bacterial competitiveness during infection.

2.50
Hdl Handle:
http://hdl.handle.net/10033/345376
Title:
Polyketide synthase (PKS) reduces fusion of Legionella pneumophila-containing vacuoles with lysosomes and contributes to bacterial competitiveness during infection.
Authors:
Shevchuk, Olga; Pägelow, Dennis; Rasch, Janine; Döhrmann, Simon; Günther, Gabriele; Hoppe, Julia; Ünal, Can Murat; Bronietzki, Marc; Gutierrez, Maximiliano Gabriel; Steinert, Michael
Abstract:
L. 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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Polyketide 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.
Journal:
International journal of medical microbiology : IJMM
Issue Date:
Nov-2014
URI:
http://hdl.handle.net/10033/345376
DOI:
10.1016/j.ijmm.2014.08.010
PubMed ID:
25218702
Type:
Article
Language:
en
ISSN:
1618-0607
Appears in Collections:
publications of the research group cellular proteom research (CPRO)

Full metadata record

DC FieldValue Language
dc.contributor.authorShevchuk, Olgaen
dc.contributor.authorPägelow, Dennisen
dc.contributor.authorRasch, Janineen
dc.contributor.authorDöhrmann, Simonen
dc.contributor.authorGünther, Gabrieleen
dc.contributor.authorHoppe, Juliaen
dc.contributor.authorÜnal, Can Muraten
dc.contributor.authorBronietzki, Marcen
dc.contributor.authorGutierrez, Maximiliano Gabrielen
dc.contributor.authorSteinert, Michaelen
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.en
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
This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.