The GBP1 microcapsule interferes with IcsA-dependent septin cage assembly around Shigella flexneri

ABSTRACT Many cytosolic bacterial pathogens hijack the host actin polymerization machinery to form actin tails that promote direct cell-to-cell spread, enabling these pathogens to avoid extracellular immune defenses. However, these pathogens are still susceptible to intracellular cell-autonomous imm...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Pathogens and Disease 2021-07, Vol.79 (5), p.1
Hauptverfasser: Kutsch, Miriam, González-Prieto, Coral, Lesser, Cammie F, Coers, Jörn
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext bestellen
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page
container_issue 5
container_start_page 1
container_title Pathogens and Disease
container_volume 79
creator Kutsch, Miriam
González-Prieto, Coral
Lesser, Cammie F
Coers, Jörn
description ABSTRACT Many cytosolic bacterial pathogens hijack the host actin polymerization machinery to form actin tails that promote direct cell-to-cell spread, enabling these pathogens to avoid extracellular immune defenses. However, these pathogens are still susceptible to intracellular cell-autonomous immune responses that restrict bacterial actin-based motility. Two classes of cytosolic antimotility factors, septins and guanylate-binding proteins (GBPs), have recently been established to block actin tail formation by the human-adapted bacterial pathogen Shigella flexneri. Both septin cages and GBP1 microcapsules restrict S. flexneri cell-to-cell spread by blocking S. flexneri actin-based motility. While septins assemble into cage-like structures around immobile S. flexneri, GBP1 forms microcapsules around both motile and immobile bacteria. The interplay between these two defense programs remains elusive. Here, we demonstrate that GBP1 microcapsules block septin cage assembly, likely by interfering with the function of S. flexneri IcsA, the outer membrane protein that promotes actin-based motility, as this protein is required for septin cage formation. However, S. flexneri that escape from GBP1 microcapsules via the activity of IpaH9.8, a type III secreted effector that promotes the degradation of GBPs, are often captured within septin cages. Thus, our studies reveal how septin cages and GBP1 microcapsules represent complementary host cell antimotility strategies. Guanylate-binding protein 1 microcapsules and septin cages are complementary antimotility factors targeting the enteric pathogen Shigella flexneri.
doi_str_mv 10.1093/femspd/ftab023
format Article
fullrecord <record><control><sourceid>gale_TOX</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8068759</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A701580125</galeid><oup_id>10.1093/femspd/ftab023</oup_id><sourcerecordid>A701580125</sourcerecordid><originalsourceid>FETCH-LOGICAL-c519t-2b3967130b6cb39719bf4aac9a0679e4be91003af77bee2b21e4d4b54b4f9ae53</originalsourceid><addsrcrecordid>eNqFkc9vFSEQxzfGxja1V4-GxIsetoXlxy4Xk2dTa5MmbWJNvBFgh_dodmGFXW3_e2nes1YvhQMT-Mx3ZvhW1RuCjwmW9MTBmKf-xM3a4Ia-qA4azGQtaPP95ZN4vzrK-RaX1XHSteJVtU9p1_FWiIPK3GwAnX-6Jmj0NkWrp7wMgHyYITlIkNEvP2_Qhc2ruocJQg9hRhmm2Qdk9RqQzhlGM9wjneISevR149cwDBq5Ae4CJP-62nN6yHC0Ow-rb5_Pbk6_1JdX5xenq8vaciLnujFUipZQbIQtYUukcUxrKzUWrQRmQBKMqXZtawAa0xBgPTOcGeakBk4Pq49b3WkxI_S2NJr0oKbkR53uVdRe_fsS_Eat40_VYdG1XBaB9zuBFH8skGc1-mwfZgkQl6waTkTHGKOsoO_-Q2_jkkIZr1CUNBIzRgp1vKXWegDlg4ulri27h_LbMYDz5X7VYsI7TBr-N6FYkXMC99g9werBcrW1XO0sLwlvn878iP8xuAAftkBcpufEfgN5rbkK</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2531290441</pqid></control><display><type>article</type><title>The GBP1 microcapsule interferes with IcsA-dependent septin cage assembly around Shigella flexneri</title><source>Oxford Open (Open Access)</source><creator>Kutsch, Miriam ; González-Prieto, Coral ; Lesser, Cammie F ; Coers, Jörn</creator><creatorcontrib>Kutsch, Miriam ; González-Prieto, Coral ; Lesser, Cammie F ; Coers, Jörn</creatorcontrib><description>ABSTRACT Many cytosolic bacterial pathogens hijack the host actin polymerization machinery to form actin tails that promote direct cell-to-cell spread, enabling these pathogens to avoid extracellular immune defenses. However, these pathogens are still susceptible to intracellular cell-autonomous immune responses that restrict bacterial actin-based motility. Two classes of cytosolic antimotility factors, septins and guanylate-binding proteins (GBPs), have recently been established to block actin tail formation by the human-adapted bacterial pathogen Shigella flexneri. Both septin cages and GBP1 microcapsules restrict S. flexneri cell-to-cell spread by blocking S. flexneri actin-based motility. While septins assemble into cage-like structures around immobile S. flexneri, GBP1 forms microcapsules around both motile and immobile bacteria. The interplay between these two defense programs remains elusive. Here, we demonstrate that GBP1 microcapsules block septin cage assembly, likely by interfering with the function of S. flexneri IcsA, the outer membrane protein that promotes actin-based motility, as this protein is required for septin cage formation. However, S. flexneri that escape from GBP1 microcapsules via the activity of IpaH9.8, a type III secreted effector that promotes the degradation of GBPs, are often captured within septin cages. Thus, our studies reveal how septin cages and GBP1 microcapsules represent complementary host cell antimotility strategies. Guanylate-binding protein 1 microcapsules and septin cages are complementary antimotility factors targeting the enteric pathogen Shigella flexneri.</description><identifier>ISSN: 2049-632X</identifier><identifier>EISSN: 2049-632X</identifier><identifier>DOI: 10.1093/femspd/ftab023</identifier><identifier>PMID: 33885766</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Actin ; Actins - metabolism ; Assembly ; Bacteria ; Bacterial Proteins - metabolism ; Binding proteins ; Biodegradation ; Blocking ; Cages ; Defense programs ; DNA-Binding Proteins - metabolism ; Editor's Choice ; GTP-Binding Proteins - genetics ; GTP-Binding Proteins - immunology ; GTP-Binding Proteins - metabolism ; HeLa Cells ; Host-bacteria relationships ; Host-Pathogen Interactions - immunology ; Humans ; Immune response ; Membrane proteins ; Microbiological research ; Microcapsules ; Motility ; Pathogens ; Physiological aspects ; Proteins ; Septin ; Septins - metabolism ; Shigella flexneri ; Shigella flexneri - immunology ; Shigella flexneri - metabolism ; Shigella flexneri - pathogenicity ; Structure ; Transcription Factors - metabolism</subject><ispartof>Pathogens and Disease, 2021-07, Vol.79 (5), p.1</ispartof><rights>The Author(s) 2021. Published by Oxford University Press on behalf of FEMS. 2021</rights><rights>The Author(s) 2021. Published by Oxford University Press on behalf of FEMS.</rights><rights>COPYRIGHT 2021 Oxford University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c519t-2b3967130b6cb39719bf4aac9a0679e4be91003af77bee2b21e4d4b54b4f9ae53</citedby><cites>FETCH-LOGICAL-c519t-2b3967130b6cb39719bf4aac9a0679e4be91003af77bee2b21e4d4b54b4f9ae53</cites><orcidid>0000-0001-8707-4608 ; 0000-0002-9346-2196</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/PMC8068759/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068759/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1604,27924,27925,53791,53793</link.rule.ids><linktorsrc>$$Uhttps://dx.doi.org/10.1093/femspd/ftab023$$EView_record_in_Oxford_University_Press$$FView_record_in_$$GOxford_University_Press</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33885766$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kutsch, Miriam</creatorcontrib><creatorcontrib>González-Prieto, Coral</creatorcontrib><creatorcontrib>Lesser, Cammie F</creatorcontrib><creatorcontrib>Coers, Jörn</creatorcontrib><title>The GBP1 microcapsule interferes with IcsA-dependent septin cage assembly around Shigella flexneri</title><title>Pathogens and Disease</title><addtitle>Pathog Dis</addtitle><description>ABSTRACT Many cytosolic bacterial pathogens hijack the host actin polymerization machinery to form actin tails that promote direct cell-to-cell spread, enabling these pathogens to avoid extracellular immune defenses. However, these pathogens are still susceptible to intracellular cell-autonomous immune responses that restrict bacterial actin-based motility. Two classes of cytosolic antimotility factors, septins and guanylate-binding proteins (GBPs), have recently been established to block actin tail formation by the human-adapted bacterial pathogen Shigella flexneri. Both septin cages and GBP1 microcapsules restrict S. flexneri cell-to-cell spread by blocking S. flexneri actin-based motility. While septins assemble into cage-like structures around immobile S. flexneri, GBP1 forms microcapsules around both motile and immobile bacteria. The interplay between these two defense programs remains elusive. Here, we demonstrate that GBP1 microcapsules block septin cage assembly, likely by interfering with the function of S. flexneri IcsA, the outer membrane protein that promotes actin-based motility, as this protein is required for septin cage formation. However, S. flexneri that escape from GBP1 microcapsules via the activity of IpaH9.8, a type III secreted effector that promotes the degradation of GBPs, are often captured within septin cages. Thus, our studies reveal how septin cages and GBP1 microcapsules represent complementary host cell antimotility strategies. Guanylate-binding protein 1 microcapsules and septin cages are complementary antimotility factors targeting the enteric pathogen Shigella flexneri.</description><subject>Actin</subject><subject>Actins - metabolism</subject><subject>Assembly</subject><subject>Bacteria</subject><subject>Bacterial Proteins - metabolism</subject><subject>Binding proteins</subject><subject>Biodegradation</subject><subject>Blocking</subject><subject>Cages</subject><subject>Defense programs</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Editor's Choice</subject><subject>GTP-Binding Proteins - genetics</subject><subject>GTP-Binding Proteins - immunology</subject><subject>GTP-Binding Proteins - metabolism</subject><subject>HeLa Cells</subject><subject>Host-bacteria relationships</subject><subject>Host-Pathogen Interactions - immunology</subject><subject>Humans</subject><subject>Immune response</subject><subject>Membrane proteins</subject><subject>Microbiological research</subject><subject>Microcapsules</subject><subject>Motility</subject><subject>Pathogens</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>Septin</subject><subject>Septins - metabolism</subject><subject>Shigella flexneri</subject><subject>Shigella flexneri - immunology</subject><subject>Shigella flexneri - metabolism</subject><subject>Shigella flexneri - pathogenicity</subject><subject>Structure</subject><subject>Transcription Factors - metabolism</subject><issn>2049-632X</issn><issn>2049-632X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkc9vFSEQxzfGxja1V4-GxIsetoXlxy4Xk2dTa5MmbWJNvBFgh_dodmGFXW3_e2nes1YvhQMT-Mx3ZvhW1RuCjwmW9MTBmKf-xM3a4Ia-qA4azGQtaPP95ZN4vzrK-RaX1XHSteJVtU9p1_FWiIPK3GwAnX-6Jmj0NkWrp7wMgHyYITlIkNEvP2_Qhc2ruocJQg9hRhmm2Qdk9RqQzhlGM9wjneISevR149cwDBq5Ae4CJP-62nN6yHC0Ow-rb5_Pbk6_1JdX5xenq8vaciLnujFUipZQbIQtYUukcUxrKzUWrQRmQBKMqXZtawAa0xBgPTOcGeakBk4Pq49b3WkxI_S2NJr0oKbkR53uVdRe_fsS_Eat40_VYdG1XBaB9zuBFH8skGc1-mwfZgkQl6waTkTHGKOsoO_-Q2_jkkIZr1CUNBIzRgp1vKXWegDlg4ulri27h_LbMYDz5X7VYsI7TBr-N6FYkXMC99g9werBcrW1XO0sLwlvn878iP8xuAAftkBcpufEfgN5rbkK</recordid><startdate>20210701</startdate><enddate>20210701</enddate><creator>Kutsch, Miriam</creator><creator>González-Prieto, Coral</creator><creator>Lesser, Cammie F</creator><creator>Coers, Jörn</creator><general>Oxford University Press</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>IAO</scope><scope>3V.</scope><scope>7T7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8707-4608</orcidid><orcidid>https://orcid.org/0000-0002-9346-2196</orcidid></search><sort><creationdate>20210701</creationdate><title>The GBP1 microcapsule interferes with IcsA-dependent septin cage assembly around Shigella flexneri</title><author>Kutsch, Miriam ; González-Prieto, Coral ; Lesser, Cammie F ; Coers, Jörn</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c519t-2b3967130b6cb39719bf4aac9a0679e4be91003af77bee2b21e4d4b54b4f9ae53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Actin</topic><topic>Actins - metabolism</topic><topic>Assembly</topic><topic>Bacteria</topic><topic>Bacterial Proteins - metabolism</topic><topic>Binding proteins</topic><topic>Biodegradation</topic><topic>Blocking</topic><topic>Cages</topic><topic>Defense programs</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Editor's Choice</topic><topic>GTP-Binding Proteins - genetics</topic><topic>GTP-Binding Proteins - immunology</topic><topic>GTP-Binding Proteins - metabolism</topic><topic>HeLa Cells</topic><topic>Host-bacteria relationships</topic><topic>Host-Pathogen Interactions - immunology</topic><topic>Humans</topic><topic>Immune response</topic><topic>Membrane proteins</topic><topic>Microbiological research</topic><topic>Microcapsules</topic><topic>Motility</topic><topic>Pathogens</topic><topic>Physiological aspects</topic><topic>Proteins</topic><topic>Septin</topic><topic>Septins - metabolism</topic><topic>Shigella flexneri</topic><topic>Shigella flexneri - immunology</topic><topic>Shigella flexneri - metabolism</topic><topic>Shigella flexneri - pathogenicity</topic><topic>Structure</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kutsch, Miriam</creatorcontrib><creatorcontrib>González-Prieto, Coral</creatorcontrib><creatorcontrib>Lesser, Cammie F</creatorcontrib><creatorcontrib>Coers, Jörn</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale Academic OneFile Select</collection><collection>ProQuest Central (Corporate)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Health &amp; Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pathogens and Disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Kutsch, Miriam</au><au>González-Prieto, Coral</au><au>Lesser, Cammie F</au><au>Coers, Jörn</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The GBP1 microcapsule interferes with IcsA-dependent septin cage assembly around Shigella flexneri</atitle><jtitle>Pathogens and Disease</jtitle><addtitle>Pathog Dis</addtitle><date>2021-07-01</date><risdate>2021</risdate><volume>79</volume><issue>5</issue><spage>1</spage><pages>1-</pages><issn>2049-632X</issn><eissn>2049-632X</eissn><abstract>ABSTRACT Many cytosolic bacterial pathogens hijack the host actin polymerization machinery to form actin tails that promote direct cell-to-cell spread, enabling these pathogens to avoid extracellular immune defenses. However, these pathogens are still susceptible to intracellular cell-autonomous immune responses that restrict bacterial actin-based motility. Two classes of cytosolic antimotility factors, septins and guanylate-binding proteins (GBPs), have recently been established to block actin tail formation by the human-adapted bacterial pathogen Shigella flexneri. Both septin cages and GBP1 microcapsules restrict S. flexneri cell-to-cell spread by blocking S. flexneri actin-based motility. While septins assemble into cage-like structures around immobile S. flexneri, GBP1 forms microcapsules around both motile and immobile bacteria. The interplay between these two defense programs remains elusive. Here, we demonstrate that GBP1 microcapsules block septin cage assembly, likely by interfering with the function of S. flexneri IcsA, the outer membrane protein that promotes actin-based motility, as this protein is required for septin cage formation. However, S. flexneri that escape from GBP1 microcapsules via the activity of IpaH9.8, a type III secreted effector that promotes the degradation of GBPs, are often captured within septin cages. Thus, our studies reveal how septin cages and GBP1 microcapsules represent complementary host cell antimotility strategies. Guanylate-binding protein 1 microcapsules and septin cages are complementary antimotility factors targeting the enteric pathogen Shigella flexneri.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>33885766</pmid><doi>10.1093/femspd/ftab023</doi><orcidid>https://orcid.org/0000-0001-8707-4608</orcidid><orcidid>https://orcid.org/0000-0002-9346-2196</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext_linktorsrc
identifier ISSN: 2049-632X
ispartof Pathogens and Disease, 2021-07, Vol.79 (5), p.1
issn 2049-632X
2049-632X
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8068759
source Oxford Open (Open Access)
subjects Actin
Actins - metabolism
Assembly
Bacteria
Bacterial Proteins - metabolism
Binding proteins
Biodegradation
Blocking
Cages
Defense programs
DNA-Binding Proteins - metabolism
Editor's Choice
GTP-Binding Proteins - genetics
GTP-Binding Proteins - immunology
GTP-Binding Proteins - metabolism
HeLa Cells
Host-bacteria relationships
Host-Pathogen Interactions - immunology
Humans
Immune response
Membrane proteins
Microbiological research
Microcapsules
Motility
Pathogens
Physiological aspects
Proteins
Septin
Septins - metabolism
Shigella flexneri
Shigella flexneri - immunology
Shigella flexneri - metabolism
Shigella flexneri - pathogenicity
Structure
Transcription Factors - metabolism
title The GBP1 microcapsule interferes with IcsA-dependent septin cage assembly around Shigella flexneri
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T18%3A25%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_TOX&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20GBP1%20microcapsule%20interferes%20with%20IcsA-dependent%20septin%20cage%20assembly%20around%20Shigella%20flexneri&rft.jtitle=Pathogens%20and%20Disease&rft.au=Kutsch,%20Miriam&rft.date=2021-07-01&rft.volume=79&rft.issue=5&rft.spage=1&rft.pages=1-&rft.issn=2049-632X&rft.eissn=2049-632X&rft_id=info:doi/10.1093/femspd/ftab023&rft_dat=%3Cgale_TOX%3EA701580125%3C/gale_TOX%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2531290441&rft_id=info:pmid/33885766&rft_galeid=A701580125&rft_oup_id=10.1093/femspd/ftab023&rfr_iscdi=true