Legionella‐ and host‐driven lipid flux at LCV‐ER membrane contact sites promotes vacuole remodeling
Legionella pneumophila replicates in macrophages and amoeba within a unique compartment, the Legionella ‐containing vacuole (LCV). Hallmarks of LCV formation are the phosphoinositide lipid conversion from PtdIns(3) P to PtdIns(4) P , fusion with ER‐derived vesicles and a tight association with the E...
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| creator | Vormittag, Simone Hüsler, Dario Haneburger, Ina Kroniger, Tobias Anand, Aby Prantl, Manuel Barisch, Caroline Maaß, Sandra Becher, Dörte Letourneur, François Hilbi, Hubert |
| description | Legionella pneumophila
replicates in macrophages and amoeba within a unique compartment, the
Legionella
‐containing vacuole (LCV). Hallmarks of LCV formation are the phosphoinositide lipid conversion from PtdIns(3)
P
to PtdIns(4)
P
, fusion with ER‐derived vesicles and a tight association with the ER. Proteomics of purified LCVs indicate the presence of membrane contact sites (MCS) proteins possibly implicated in lipid exchange. Using dually fluorescence‐labeled
Dictyostelium discoideum
amoeba, we reveal that VAMP‐associated protein (Vap) and the PtdIns(4)
P
4‐phosphatase Sac1 localize to the ER, and Vap also localizes to the LCV membrane. Furthermore, Vap as well as Sac1 promote intracellular replication of
L. pneumophila
and LCV remodeling. Oxysterol binding proteins (OSBPs) preferentially localize to the ER (OSBP8) or the LCV membrane (OSBP11), respectively, and restrict (OSBP8) or promote (OSBP11) bacterial replication and LCV expansion. The sterol probes GFP‐D4H* and filipin indicate that sterols are rapidly depleted from LCVs, while PtdIns(4)
P
accumulates. In addition to Sac1, the PtdIns(4)
P
‐subverting
L. pneumophila
effector proteins LepB and SidC also support LCV remodeling. Taken together, the
Legionella
‐ and host cell‐driven PtdIns(4)
P
gradient at LCV‐ER MCSs promotes Vap‐, OSBP‐ and Sac1‐dependent pathogen vacuole maturation.
Synopsis
Legionella pneumophila
replicates intracellularly within a unique “
Legionella
‐containing vacuole” (LCV). Dually fluorescence‐labeled
Dictyostelium discoideum
amoeba reveal that LCVs and the ER form membrane contact sites and
Legionella
‐ as well as host cell‐driven lipid flux promotes pathogen vacuole remodeling.
The
Legionella
‐containing vacuole (LCV) engages in membrane contact sites (MCS) with the ER.
The MCS components VAMP‐associated protein (Vap), oxysterol binding proteins (OSBPs), and the PtdIns(4)
P
4‐phosphatase Sac1 localize to the ER and/or the LCV membrane.
Host cell factors (Vap, OSBPs, Sac1) as well as bacterial effector proteins (LepB, SidC) modulate lipid exchange, LCV remodelling and intracellular growth of
L. pneumophila
.
Graphical Abstract
Legionella pneumophila
replicates intracellularly within a unique “
Legionella
‐containing vacuole” (LCV). Dually fluorescence‐labeled
Dictyostelium discoideum
amoeba reveal that LCVs and the ER form membrane contact sites and
Legionella
‐ as well as host cell‐driven lipid flux promotes pathogen vacuole remodeling. |
| doi_str_mv | 10.15252/embr.202256007 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_C6C</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9986823</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2760173390</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5137-9c9bfc6edb475e4aad094d8679d594f56a6c3272e887dc9419e7f9ef23122f5b3</originalsourceid><addsrcrecordid>eNqFkc2KFDEUhQtRnHF07U4Cbtz0TH4qlcSFoE37Ay3CoOIupJJbPRmqkp6kqnV2PoLP6JOYttt2FMRVLtzvnpx7T1U9JPiUcMrpGQxtOqWYUt5gLG5Vx6Ru1IwRIW_va0rJp6PqXs6XGGOuhLxbHbGGS1kLdVz5Jax8DND35vvXb8gEhy5iHkvtkt9AQL1fe4e6fvqCzIiW84-ltThHw_ZjEwDZGEZjR5T9CBmtUxzittgYO8UeUIIhOuh9WN2v7nSmz_Bg_55UH14u3s9fz5bvXr2ZP1_OLCdMzJRVbWcbcG0tONTGOKxqJxuhHFd1xxvTWEYFBSmFs6omCkSnoKOMUNrxlp1Uz3a666kdwFkIYzK9Xic_mHSto_H6z07wF3oVN1op2UjKisCTvUCKVxPkUQ8-2-2FAsQpayoaTARjChf08V_oZZxSKOsVSlIpGVF1oc52lE0x5wTdwQzB-meMentNfYixTDy6ucOB_5VbAZ7ugM--h-v_6enF2xfnN9XxbjiXubCC9Nv1vwz9ADe2vnk</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2782883194</pqid></control><display><type>article</type><title>Legionella‐ and host‐driven lipid flux at LCV‐ER membrane contact sites promotes vacuole remodeling</title><source>Springer Nature OA Free Journals</source><creator>Vormittag, Simone ; Hüsler, Dario ; Haneburger, Ina ; Kroniger, Tobias ; Anand, Aby ; Prantl, Manuel ; Barisch, Caroline ; Maaß, Sandra ; Becher, Dörte ; Letourneur, François ; Hilbi, Hubert</creator><creatorcontrib>Vormittag, Simone ; Hüsler, Dario ; Haneburger, Ina ; Kroniger, Tobias ; Anand, Aby ; Prantl, Manuel ; Barisch, Caroline ; Maaß, Sandra ; Becher, Dörte ; Letourneur, François ; Hilbi, Hubert</creatorcontrib><description>Legionella pneumophila
replicates in macrophages and amoeba within a unique compartment, the
Legionella
‐containing vacuole (LCV). Hallmarks of LCV formation are the phosphoinositide lipid conversion from PtdIns(3)
P
to PtdIns(4)
P
, fusion with ER‐derived vesicles and a tight association with the ER. Proteomics of purified LCVs indicate the presence of membrane contact sites (MCS) proteins possibly implicated in lipid exchange. Using dually fluorescence‐labeled
Dictyostelium discoideum
amoeba, we reveal that VAMP‐associated protein (Vap) and the PtdIns(4)
P
4‐phosphatase Sac1 localize to the ER, and Vap also localizes to the LCV membrane. Furthermore, Vap as well as Sac1 promote intracellular replication of
L. pneumophila
and LCV remodeling. Oxysterol binding proteins (OSBPs) preferentially localize to the ER (OSBP8) or the LCV membrane (OSBP11), respectively, and restrict (OSBP8) or promote (OSBP11) bacterial replication and LCV expansion. The sterol probes GFP‐D4H* and filipin indicate that sterols are rapidly depleted from LCVs, while PtdIns(4)
P
accumulates. In addition to Sac1, the PtdIns(4)
P
‐subverting
L. pneumophila
effector proteins LepB and SidC also support LCV remodeling. Taken together, the
Legionella
‐ and host cell‐driven PtdIns(4)
P
gradient at LCV‐ER MCSs promotes Vap‐, OSBP‐ and Sac1‐dependent pathogen vacuole maturation.
Synopsis
Legionella pneumophila
replicates intracellularly within a unique “
Legionella
‐containing vacuole” (LCV). Dually fluorescence‐labeled
Dictyostelium discoideum
amoeba reveal that LCVs and the ER form membrane contact sites and
Legionella
‐ as well as host cell‐driven lipid flux promotes pathogen vacuole remodeling.
The
Legionella
‐containing vacuole (LCV) engages in membrane contact sites (MCS) with the ER.
The MCS components VAMP‐associated protein (Vap), oxysterol binding proteins (OSBPs), and the PtdIns(4)
P
4‐phosphatase Sac1 localize to the ER and/or the LCV membrane.
Host cell factors (Vap, OSBPs, Sac1) as well as bacterial effector proteins (LepB, SidC) modulate lipid exchange, LCV remodelling and intracellular growth of
L. pneumophila
.
Graphical Abstract
Legionella pneumophila
replicates intracellularly within a unique “
Legionella
‐containing vacuole” (LCV). Dually fluorescence‐labeled
Dictyostelium discoideum
amoeba reveal that LCVs and the ER form membrane contact sites and
Legionella
‐ as well as host cell‐driven lipid flux promotes pathogen vacuole remodeling.</description><identifier>ISSN: 1469-221X</identifier><identifier>EISSN: 1469-3178</identifier><identifier>DOI: 10.15252/embr.202256007</identifier><identifier>PMID: 36588479</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Amoeba ; Atlastin ; Bacterial Proteins - metabolism ; Binding ; Dictyostelium - microbiology ; Dictyostelium discoideum ; EMBO20 ; EMBO23 ; EMBO57 ; Fluorescence ; Intracellular ; Legionella ; Legionella - metabolism ; Legionella pneumophila ; Legionnaires' disease ; Legionnaires' disease bacterium ; Life Sciences ; Lipids ; Macrophages ; Membrane Proteins - metabolism ; Membranes ; oxysterol binding protein ; Pathogens ; Phosphatase ; Phosphatidylinositols - metabolism ; Proteins ; Proteomics ; Replication ; Sac1 phosphoinositide phosphatase ; Sterols ; Vacuoles - metabolism ; Vesicle fusion</subject><ispartof>EMBO reports, 2023-03, Vol.24 (3), p.e56007-n/a</ispartof><rights>The Author(s) 2022</rights><rights>2022 The Authors.</rights><rights>2023 EMBO</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5137-9c9bfc6edb475e4aad094d8679d594f56a6c3272e887dc9419e7f9ef23122f5b3</citedby><cites>FETCH-LOGICAL-c5137-9c9bfc6edb475e4aad094d8679d594f56a6c3272e887dc9419e7f9ef23122f5b3</cites><orcidid>0000-0002-9630-5735 ; 0000-0003-2232-6127 ; 0000-0002-6611-1956 ; 0000-0002-5462-9301</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986823/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986823/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,724,777,781,882,1412,1428,27905,27906,41101,42170,45555,45556,46390,46814,51557,53772,53774</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.15252/embr.202256007$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36588479$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vormittag, Simone</creatorcontrib><creatorcontrib>Hüsler, Dario</creatorcontrib><creatorcontrib>Haneburger, Ina</creatorcontrib><creatorcontrib>Kroniger, Tobias</creatorcontrib><creatorcontrib>Anand, Aby</creatorcontrib><creatorcontrib>Prantl, Manuel</creatorcontrib><creatorcontrib>Barisch, Caroline</creatorcontrib><creatorcontrib>Maaß, Sandra</creatorcontrib><creatorcontrib>Becher, Dörte</creatorcontrib><creatorcontrib>Letourneur, François</creatorcontrib><creatorcontrib>Hilbi, Hubert</creatorcontrib><title>Legionella‐ and host‐driven lipid flux at LCV‐ER membrane contact sites promotes vacuole remodeling</title><title>EMBO reports</title><addtitle>EMBO Rep</addtitle><addtitle>EMBO Rep</addtitle><description>Legionella pneumophila
replicates in macrophages and amoeba within a unique compartment, the
Legionella
‐containing vacuole (LCV). Hallmarks of LCV formation are the phosphoinositide lipid conversion from PtdIns(3)
P
to PtdIns(4)
P
, fusion with ER‐derived vesicles and a tight association with the ER. Proteomics of purified LCVs indicate the presence of membrane contact sites (MCS) proteins possibly implicated in lipid exchange. Using dually fluorescence‐labeled
Dictyostelium discoideum
amoeba, we reveal that VAMP‐associated protein (Vap) and the PtdIns(4)
P
4‐phosphatase Sac1 localize to the ER, and Vap also localizes to the LCV membrane. Furthermore, Vap as well as Sac1 promote intracellular replication of
L. pneumophila
and LCV remodeling. Oxysterol binding proteins (OSBPs) preferentially localize to the ER (OSBP8) or the LCV membrane (OSBP11), respectively, and restrict (OSBP8) or promote (OSBP11) bacterial replication and LCV expansion. The sterol probes GFP‐D4H* and filipin indicate that sterols are rapidly depleted from LCVs, while PtdIns(4)
P
accumulates. In addition to Sac1, the PtdIns(4)
P
‐subverting
L. pneumophila
effector proteins LepB and SidC also support LCV remodeling. Taken together, the
Legionella
‐ and host cell‐driven PtdIns(4)
P
gradient at LCV‐ER MCSs promotes Vap‐, OSBP‐ and Sac1‐dependent pathogen vacuole maturation.
Synopsis
Legionella pneumophila
replicates intracellularly within a unique “
Legionella
‐containing vacuole” (LCV). Dually fluorescence‐labeled
Dictyostelium discoideum
amoeba reveal that LCVs and the ER form membrane contact sites and
Legionella
‐ as well as host cell‐driven lipid flux promotes pathogen vacuole remodeling.
The
Legionella
‐containing vacuole (LCV) engages in membrane contact sites (MCS) with the ER.
The MCS components VAMP‐associated protein (Vap), oxysterol binding proteins (OSBPs), and the PtdIns(4)
P
4‐phosphatase Sac1 localize to the ER and/or the LCV membrane.
Host cell factors (Vap, OSBPs, Sac1) as well as bacterial effector proteins (LepB, SidC) modulate lipid exchange, LCV remodelling and intracellular growth of
L. pneumophila
.
Graphical Abstract
Legionella pneumophila
replicates intracellularly within a unique “
Legionella
‐containing vacuole” (LCV). Dually fluorescence‐labeled
Dictyostelium discoideum
amoeba reveal that LCVs and the ER form membrane contact sites and
Legionella
‐ as well as host cell‐driven lipid flux promotes pathogen vacuole remodeling.</description><subject>Amoeba</subject><subject>Atlastin</subject><subject>Bacterial Proteins - metabolism</subject><subject>Binding</subject><subject>Dictyostelium - microbiology</subject><subject>Dictyostelium discoideum</subject><subject>EMBO20</subject><subject>EMBO23</subject><subject>EMBO57</subject><subject>Fluorescence</subject><subject>Intracellular</subject><subject>Legionella</subject><subject>Legionella - metabolism</subject><subject>Legionella pneumophila</subject><subject>Legionnaires' disease</subject><subject>Legionnaires' disease bacterium</subject><subject>Life Sciences</subject><subject>Lipids</subject><subject>Macrophages</subject><subject>Membrane Proteins - metabolism</subject><subject>Membranes</subject><subject>oxysterol binding protein</subject><subject>Pathogens</subject><subject>Phosphatase</subject><subject>Phosphatidylinositols - metabolism</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Replication</subject><subject>Sac1 phosphoinositide phosphatase</subject><subject>Sterols</subject><subject>Vacuoles - metabolism</subject><subject>Vesicle fusion</subject><issn>1469-221X</issn><issn>1469-3178</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2KFDEUhQtRnHF07U4Cbtz0TH4qlcSFoE37Ay3CoOIupJJbPRmqkp6kqnV2PoLP6JOYttt2FMRVLtzvnpx7T1U9JPiUcMrpGQxtOqWYUt5gLG5Vx6Ru1IwRIW_va0rJp6PqXs6XGGOuhLxbHbGGS1kLdVz5Jax8DND35vvXb8gEhy5iHkvtkt9AQL1fe4e6fvqCzIiW84-ltThHw_ZjEwDZGEZjR5T9CBmtUxzittgYO8UeUIIhOuh9WN2v7nSmz_Bg_55UH14u3s9fz5bvXr2ZP1_OLCdMzJRVbWcbcG0tONTGOKxqJxuhHFd1xxvTWEYFBSmFs6omCkSnoKOMUNrxlp1Uz3a666kdwFkIYzK9Xic_mHSto_H6z07wF3oVN1op2UjKisCTvUCKVxPkUQ8-2-2FAsQpayoaTARjChf08V_oZZxSKOsVSlIpGVF1oc52lE0x5wTdwQzB-meMentNfYixTDy6ucOB_5VbAZ7ugM--h-v_6enF2xfnN9XxbjiXubCC9Nv1vwz9ADe2vnk</recordid><startdate>20230306</startdate><enddate>20230306</enddate><creator>Vormittag, Simone</creator><creator>Hüsler, Dario</creator><creator>Haneburger, Ina</creator><creator>Kroniger, Tobias</creator><creator>Anand, Aby</creator><creator>Prantl, Manuel</creator><creator>Barisch, Caroline</creator><creator>Maaß, Sandra</creator><creator>Becher, Dörte</creator><creator>Letourneur, François</creator><creator>Hilbi, Hubert</creator><general>Nature Publishing Group UK</general><general>Blackwell Publishing Ltd</general><general>John Wiley and Sons Inc</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>7QL</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9630-5735</orcidid><orcidid>https://orcid.org/0000-0003-2232-6127</orcidid><orcidid>https://orcid.org/0000-0002-6611-1956</orcidid><orcidid>https://orcid.org/0000-0002-5462-9301</orcidid></search><sort><creationdate>20230306</creationdate><title>Legionella‐ and host‐driven lipid flux at LCV‐ER membrane contact sites promotes vacuole remodeling</title><author>Vormittag, Simone ; Hüsler, Dario ; Haneburger, Ina ; Kroniger, Tobias ; Anand, Aby ; Prantl, Manuel ; Barisch, Caroline ; Maaß, Sandra ; Becher, Dörte ; Letourneur, François ; Hilbi, Hubert</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5137-9c9bfc6edb475e4aad094d8679d594f56a6c3272e887dc9419e7f9ef23122f5b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Amoeba</topic><topic>Atlastin</topic><topic>Bacterial Proteins - metabolism</topic><topic>Binding</topic><topic>Dictyostelium - microbiology</topic><topic>Dictyostelium discoideum</topic><topic>EMBO20</topic><topic>EMBO23</topic><topic>EMBO57</topic><topic>Fluorescence</topic><topic>Intracellular</topic><topic>Legionella</topic><topic>Legionella - metabolism</topic><topic>Legionella pneumophila</topic><topic>Legionnaires' disease</topic><topic>Legionnaires' disease bacterium</topic><topic>Life Sciences</topic><topic>Lipids</topic><topic>Macrophages</topic><topic>Membrane Proteins - metabolism</topic><topic>Membranes</topic><topic>oxysterol binding protein</topic><topic>Pathogens</topic><topic>Phosphatase</topic><topic>Phosphatidylinositols - metabolism</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>Replication</topic><topic>Sac1 phosphoinositide phosphatase</topic><topic>Sterols</topic><topic>Vacuoles - metabolism</topic><topic>Vesicle fusion</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vormittag, Simone</creatorcontrib><creatorcontrib>Hüsler, Dario</creatorcontrib><creatorcontrib>Haneburger, Ina</creatorcontrib><creatorcontrib>Kroniger, Tobias</creatorcontrib><creatorcontrib>Anand, Aby</creatorcontrib><creatorcontrib>Prantl, Manuel</creatorcontrib><creatorcontrib>Barisch, Caroline</creatorcontrib><creatorcontrib>Maaß, Sandra</creatorcontrib><creatorcontrib>Becher, Dörte</creatorcontrib><creatorcontrib>Letourneur, François</creatorcontrib><creatorcontrib>Hilbi, Hubert</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>EMBO reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Vormittag, Simone</au><au>Hüsler, Dario</au><au>Haneburger, Ina</au><au>Kroniger, Tobias</au><au>Anand, Aby</au><au>Prantl, Manuel</au><au>Barisch, Caroline</au><au>Maaß, Sandra</au><au>Becher, Dörte</au><au>Letourneur, François</au><au>Hilbi, Hubert</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Legionella‐ and host‐driven lipid flux at LCV‐ER membrane contact sites promotes vacuole remodeling</atitle><jtitle>EMBO reports</jtitle><stitle>EMBO Rep</stitle><addtitle>EMBO Rep</addtitle><date>2023-03-06</date><risdate>2023</risdate><volume>24</volume><issue>3</issue><spage>e56007</spage><epage>n/a</epage><pages>e56007-n/a</pages><issn>1469-221X</issn><eissn>1469-3178</eissn><abstract>Legionella pneumophila
replicates in macrophages and amoeba within a unique compartment, the
Legionella
‐containing vacuole (LCV). Hallmarks of LCV formation are the phosphoinositide lipid conversion from PtdIns(3)
P
to PtdIns(4)
P
, fusion with ER‐derived vesicles and a tight association with the ER. Proteomics of purified LCVs indicate the presence of membrane contact sites (MCS) proteins possibly implicated in lipid exchange. Using dually fluorescence‐labeled
Dictyostelium discoideum
amoeba, we reveal that VAMP‐associated protein (Vap) and the PtdIns(4)
P
4‐phosphatase Sac1 localize to the ER, and Vap also localizes to the LCV membrane. Furthermore, Vap as well as Sac1 promote intracellular replication of
L. pneumophila
and LCV remodeling. Oxysterol binding proteins (OSBPs) preferentially localize to the ER (OSBP8) or the LCV membrane (OSBP11), respectively, and restrict (OSBP8) or promote (OSBP11) bacterial replication and LCV expansion. The sterol probes GFP‐D4H* and filipin indicate that sterols are rapidly depleted from LCVs, while PtdIns(4)
P
accumulates. In addition to Sac1, the PtdIns(4)
P
‐subverting
L. pneumophila
effector proteins LepB and SidC also support LCV remodeling. Taken together, the
Legionella
‐ and host cell‐driven PtdIns(4)
P
gradient at LCV‐ER MCSs promotes Vap‐, OSBP‐ and Sac1‐dependent pathogen vacuole maturation.
Synopsis
Legionella pneumophila
replicates intracellularly within a unique “
Legionella
‐containing vacuole” (LCV). Dually fluorescence‐labeled
Dictyostelium discoideum
amoeba reveal that LCVs and the ER form membrane contact sites and
Legionella
‐ as well as host cell‐driven lipid flux promotes pathogen vacuole remodeling.
The
Legionella
‐containing vacuole (LCV) engages in membrane contact sites (MCS) with the ER.
The MCS components VAMP‐associated protein (Vap), oxysterol binding proteins (OSBPs), and the PtdIns(4)
P
4‐phosphatase Sac1 localize to the ER and/or the LCV membrane.
Host cell factors (Vap, OSBPs, Sac1) as well as bacterial effector proteins (LepB, SidC) modulate lipid exchange, LCV remodelling and intracellular growth of
L. pneumophila
.
Graphical Abstract
Legionella pneumophila
replicates intracellularly within a unique “
Legionella
‐containing vacuole” (LCV). Dually fluorescence‐labeled
Dictyostelium discoideum
amoeba reveal that LCVs and the ER form membrane contact sites and
Legionella
‐ as well as host cell‐driven lipid flux promotes pathogen vacuole remodeling.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>36588479</pmid><doi>10.15252/embr.202256007</doi><tpages>23</tpages><orcidid>https://orcid.org/0000-0002-9630-5735</orcidid><orcidid>https://orcid.org/0000-0003-2232-6127</orcidid><orcidid>https://orcid.org/0000-0002-6611-1956</orcidid><orcidid>https://orcid.org/0000-0002-5462-9301</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext_linktorsrc |
| identifier | ISSN: 1469-221X |
| ispartof | EMBO reports, 2023-03, Vol.24 (3), p.e56007-n/a |
| issn | 1469-221X 1469-3178 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9986823 |
| source | Springer Nature OA Free Journals |
| subjects | Amoeba Atlastin Bacterial Proteins - metabolism Binding Dictyostelium - microbiology Dictyostelium discoideum EMBO20 EMBO23 EMBO57 Fluorescence Intracellular Legionella Legionella - metabolism Legionella pneumophila Legionnaires' disease Legionnaires' disease bacterium Life Sciences Lipids Macrophages Membrane Proteins - metabolism Membranes oxysterol binding protein Pathogens Phosphatase Phosphatidylinositols - metabolism Proteins Proteomics Replication Sac1 phosphoinositide phosphatase Sterols Vacuoles - metabolism Vesicle fusion |
| title | Legionella‐ and host‐driven lipid flux at LCV‐ER membrane contact sites promotes vacuole remodeling |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T00%3A09%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_C6C&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Legionella%E2%80%90%20and%20host%E2%80%90driven%20lipid%20flux%20at%20LCV%E2%80%90ER%20membrane%20contact%20sites%20promotes%20vacuole%20remodeling&rft.jtitle=EMBO%20reports&rft.au=Vormittag,%20Simone&rft.date=2023-03-06&rft.volume=24&rft.issue=3&rft.spage=e56007&rft.epage=n/a&rft.pages=e56007-n/a&rft.issn=1469-221X&rft.eissn=1469-3178&rft_id=info:doi/10.15252/embr.202256007&rft_dat=%3Cproquest_C6C%3E2760173390%3C/proquest_C6C%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2782883194&rft_id=info:pmid/36588479&rfr_iscdi=true |