Polyketide synthase (PKS) reduces fusion of Legionella pneumophila- containing vacuoles with lysosomes and contributes to bacterial competitiveness during infection
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 c...
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| Veröffentlicht in: | International journal of medical microbiology 2014-11, Vol.304 (8), p.1169-1181 |
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| container_title | International journal of medical microbiology |
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| creator | Shevchuk, Olga Pägelow, Dennis Rasch, Janine Döhrmann, Simon Günther, Gabriele Hoppe, Julia Ünal, Can Murat Bronietzki, Marc Gutierrez, Maximiliano Gabriel Steinert, Michael |
| description | 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. |
| doi_str_mv | 10.1016/j.ijmm.2014.08.010 |
| format | Article |
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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.</description><identifier>ISSN: 1438-4221</identifier><identifier>EISSN: 1618-0607</identifier><identifier>DOI: 10.1016/j.ijmm.2014.08.010</identifier><identifier>PMID: 25218702</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Bacteria ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; Cell Line ; Dictyostelium - microbiology ; DNA Transposable Elements ; Fitness ; Host-Pathogen Interactions ; Humans ; Infectious Disease ; Legionella ; Legionella pneumophila - genetics ; Legionella pneumophila - growth & development ; Legionella pneumophila - physiology ; Legionnaires' Disease - microbiology ; Lysosomes - metabolism ; Medical Education ; Monocytes - microbiology ; Mutagenesis, Insertional ; PKS ; Polyketide Synthases - genetics ; Polyketide Synthases - metabolism ; Transposon mutants ; Vacuoles - metabolism ; Vacuoles - microbiology ; Virulence ; Virulence Factors - genetics ; Virulence Factors - metabolism</subject><ispartof>International journal of medical microbiology, 2014-11, Vol.304 (8), p.1169-1181</ispartof><rights>Elsevier GmbH</rights><rights>2014 Elsevier GmbH</rights><rights>Copyright © 2014 Elsevier GmbH. 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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.</description><subject>Bacteria</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - metabolism</subject><subject>Cell Line</subject><subject>Dictyostelium - microbiology</subject><subject>DNA Transposable Elements</subject><subject>Fitness</subject><subject>Host-Pathogen Interactions</subject><subject>Humans</subject><subject>Infectious Disease</subject><subject>Legionella</subject><subject>Legionella pneumophila - genetics</subject><subject>Legionella pneumophila - growth & development</subject><subject>Legionella pneumophila - physiology</subject><subject>Legionnaires' Disease - microbiology</subject><subject>Lysosomes - metabolism</subject><subject>Medical Education</subject><subject>Monocytes - microbiology</subject><subject>Mutagenesis, Insertional</subject><subject>PKS</subject><subject>Polyketide Synthases - genetics</subject><subject>Polyketide Synthases - metabolism</subject><subject>Transposon mutants</subject><subject>Vacuoles - metabolism</subject><subject>Vacuoles - microbiology</subject><subject>Virulence</subject><subject>Virulence Factors - genetics</subject><subject>Virulence Factors - metabolism</subject><issn>1438-4221</issn><issn>1618-0607</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUsuO1DAQjBCIfcAPcEA-LocM7UcSR0JIaMVLjMRKCxI3y3E6O55N7MF2Bs3_7IfiMAsHDoiTu-Wqaruqi-IZhRUFWr_crux2mlYMqFiBXAGFB8UpraksoYbmYa4Fl6VgjJ4UZzFuAYC1vH5cnLCKUdkAOy3urvx4uMVkeyTx4NJGRyQXV5-uX5CA_WwwkmGO1jviB7LGm1zhOGqyczhPfrexoy6J8S5p66y7IXttZj9m1g-bNmQ8RB_9lFvt-l-wYLs55T550mmTMFg95otpl5-Q7B4dxkj6OSxa1g1oUp74pHg06DHi0_vzvPj67u2Xyw_l-vP7j5dv1qWpmUwlq6DhvKuFBC65YVoMsmO96agEIXQjqhbbQWA_NCga3naNqYRpqaFgpBHIz4uLo-4u-O8zxqQmG83yX4d-jorWlagbWdX1f0BZ21a84ZCh7Ag1wccYcFC7YCcdDoqCWoJUW7UEqZYgFUiVg8yk5_f6czdh_4fyO7kMeHUEYDZkbzGoaCw6g70N2TXVe_tv_dd_0c2YEzR6vMUDxq2fg8tWK6oiU6Cul1VaNokKyPT2G_8Jgr_HoQ</recordid><startdate>20141101</startdate><enddate>20141101</enddate><creator>Shevchuk, Olga</creator><creator>Pägelow, Dennis</creator><creator>Rasch, Janine</creator><creator>Döhrmann, Simon</creator><creator>Günther, Gabriele</creator><creator>Hoppe, Julia</creator><creator>Ünal, Can Murat</creator><creator>Bronietzki, Marc</creator><creator>Gutierrez, Maximiliano Gabriel</creator><creator>Steinert, Michael</creator><general>Elsevier GmbH</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QL</scope><scope>C1K</scope></search><sort><creationdate>20141101</creationdate><title>Polyketide synthase (PKS) reduces fusion of Legionella pneumophila- containing vacuoles with lysosomes and contributes to bacterial competitiveness during infection</title><author>Shevchuk, Olga ; Pägelow, Dennis ; Rasch, Janine ; Döhrmann, Simon ; Günther, Gabriele ; Hoppe, Julia ; Ünal, Can Murat ; Bronietzki, Marc ; Gutierrez, Maximiliano Gabriel ; Steinert, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c628t-250733b6480383c2a4f8b2dcb18044a7459e9f4edf7e4739b7c54c91c10c8c4e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Bacteria</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - metabolism</topic><topic>Cell Line</topic><topic>Dictyostelium - microbiology</topic><topic>DNA Transposable Elements</topic><topic>Fitness</topic><topic>Host-Pathogen Interactions</topic><topic>Humans</topic><topic>Infectious Disease</topic><topic>Legionella</topic><topic>Legionella pneumophila - genetics</topic><topic>Legionella pneumophila - growth & development</topic><topic>Legionella pneumophila - physiology</topic><topic>Legionnaires' Disease - microbiology</topic><topic>Lysosomes - metabolism</topic><topic>Medical Education</topic><topic>Monocytes - microbiology</topic><topic>Mutagenesis, Insertional</topic><topic>PKS</topic><topic>Polyketide Synthases - genetics</topic><topic>Polyketide Synthases - metabolism</topic><topic>Transposon mutants</topic><topic>Vacuoles - metabolism</topic><topic>Vacuoles - microbiology</topic><topic>Virulence</topic><topic>Virulence Factors - genetics</topic><topic>Virulence Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shevchuk, Olga</creatorcontrib><creatorcontrib>Pägelow, Dennis</creatorcontrib><creatorcontrib>Rasch, Janine</creatorcontrib><creatorcontrib>Döhrmann, Simon</creatorcontrib><creatorcontrib>Günther, Gabriele</creatorcontrib><creatorcontrib>Hoppe, Julia</creatorcontrib><creatorcontrib>Ünal, Can Murat</creatorcontrib><creatorcontrib>Bronietzki, Marc</creatorcontrib><creatorcontrib>Gutierrez, Maximiliano Gabriel</creatorcontrib><creatorcontrib>Steinert, Michael</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>International journal of medical microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shevchuk, Olga</au><au>Pägelow, Dennis</au><au>Rasch, Janine</au><au>Döhrmann, Simon</au><au>Günther, Gabriele</au><au>Hoppe, Julia</au><au>Ünal, Can Murat</au><au>Bronietzki, Marc</au><au>Gutierrez, Maximiliano Gabriel</au><au>Steinert, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polyketide synthase (PKS) reduces fusion of Legionella pneumophila- containing vacuoles with lysosomes and contributes to bacterial competitiveness during infection</atitle><jtitle>International journal of medical microbiology</jtitle><addtitle>Int J Med Microbiol</addtitle><date>2014-11-01</date><risdate>2014</risdate><volume>304</volume><issue>8</issue><spage>1169</spage><epage>1181</epage><pages>1169-1181</pages><issn>1438-4221</issn><eissn>1618-0607</eissn><abstract>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. 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| identifier | ISSN: 1438-4221 |
| ispartof | International journal of medical microbiology, 2014-11, Vol.304 (8), p.1169-1181 |
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| subjects | Bacteria Bacterial Proteins - genetics Bacterial Proteins - metabolism Cell Line Dictyostelium - microbiology DNA Transposable Elements Fitness Host-Pathogen Interactions Humans Infectious Disease Legionella Legionella pneumophila - genetics Legionella pneumophila - growth & development Legionella pneumophila - physiology Legionnaires' Disease - microbiology Lysosomes - metabolism Medical Education Monocytes - microbiology Mutagenesis, Insertional PKS Polyketide Synthases - genetics Polyketide Synthases - metabolism Transposon mutants Vacuoles - metabolism Vacuoles - microbiology Virulence Virulence Factors - genetics Virulence Factors - metabolism |
| title | Polyketide synthase (PKS) reduces fusion of Legionella pneumophila- containing vacuoles with lysosomes and contributes to bacterial competitiveness during infection |
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