{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:48:31Z","timestamp":1790095711061,"version":"4.0.1"},"reference-count":93,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00c3\u00a5det","doi-asserted-by":"publisher","award":["VR-2018-02286"],"award-info":[{"award-number":["VR-2018-02286"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00c3\u00a5det","doi-asserted-by":"publisher","award":["VR-2022-00852"],"award-info":[{"award-number":["VR-2022-00852"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00c3\u00a5det","doi-asserted-by":"publisher","award":["VR-2016-06598"],"award-info":[{"award-number":["VR-2016-06598"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00c3\u00a5det","doi-asserted-by":"publisher","award":["VR-2021-06602"],"award-info":[{"award-number":["VR-2021-06602"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007067","name":"Kempestiftelserna","doi-asserted-by":"publisher","award":["JCK-1834"],"award-info":[{"award-number":["JCK-1834"]}],"id":[{"id":"10.13039\/501100007067","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007067","name":"Kempestiftelserna","doi-asserted-by":"publisher","award":["JCK-2031.2"],"award-info":[{"award-number":["JCK-2031.2"]}],"id":[{"id":"10.13039\/501100007067","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010794","name":"Medicinska fakulteten, Ume\u00c3\u00a5 Universitet","doi-asserted-by":"publisher","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}],"id":[{"id":"10.13039\/501100010794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["417857878"],"award-info":[{"award-number":["417857878"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>A mechanistic understanding of how intracellular pathogens evade the intrinsic defenses of their host cells could open up intriguing therapeutic opportunities. Here, we applied a genome-wide genetic screening approach to investigate the nature of the defensive host cell death response suppressed by the membrane trafficking modulator CpoS, an effector protein secreted by the obligate intracellular bacterial pathogen <jats:italic><jats:italic>Chlamydia trachomatis<\/jats:italic><\/jats:italic>. Initially, this work revealed a CpoS-deficient mutant to exhibit a markedly increased dependence on host cellular synthesis of ceramides, the precursors of complex sphingolipids. Using novel microscopic reporters, we then established CpoS\u2019 role in defense evasion to occur by preserving the integrity of <jats:italic><jats:italic>Chlamydia<\/jats:italic><\/jats:italic>\u2019s parasitophorous vacuole (the inclusion) via ensuring an adequate sphingolipid supply. More specifically, we observed CpoS deficiency to destabilize inclusions, initially characterized by a release of individual bacteria into the host cell cytosol, then followed by inclusion rupture concomitant with host cell death. Exogenous addition of sphingosine stabilized CpoS-deficient inclusions, whereas disruption of host cellular ceramide synthesis destabilized wild-type inclusions. In combination, CpoS deficiency and impaired ceramide synthesis \u2013 presumably disrupting both <jats:italic><jats:italic>Chlamydia<\/jats:italic><\/jats:italic>\u2019s vesicular and non-vesicular sphingolipid supply routes \u2013 destabilized inclusions even earlier, resulting in infection clearance and host cell survival rather than host cell death. Overall, this study highlights how the vacuolar pathogen <jats:italic><jats:italic>C. trachomatis<\/jats:italic><\/jats:italic> maintains vacuole integrity by ensuring a steady sphingolipid supply, potentially offering inspiration and directions for future therapeutic strategies targeting parasitophorous vacuoles.<\/jats:p>","DOI":"10.1371\/journal.pbio.3003297","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T17:21:52Z","timestamp":1755019312000},"page":"e3003297","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genome-wide identification of modulators of Chlamydia trachomatis parasitophorous vacuole stability highlights an important role for sphingolipid supply"],"prefix":"10.1371","volume":"23","author":[{"given":"Mohammed Rizwan","family":"Babu Sait","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lana H.","family":"Jachmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6zde","family":"T\u00fcrk\u00f6z","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milica","family":"Milivojevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Llorente-S\u00e1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soniya","family":"Dhanjal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Schumacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Henriksson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naga Venkata","family":"Gayathri Vegesna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha","family":"Seddik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiia","family":"Chaban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Partha","family":"Mohanty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"\u00d6lander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samada","family":"Muraleedharan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepideh","family":"Farmand Azadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhard","family":"Kleuser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Schmierer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5607-8902","authenticated-orcid":true,"given":"Barbara S.","family":"Sixt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"issue":"1","key":"pbio.3003297.ref001","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/s41572-022-00359-5","article-title":"Trachoma","volume":"8","author":"AW Solomon","year":"2022","journal-title":"Nat Rev Dis Primers"},{"key":"pbio.3003297.ref002","first-page":"25","article-title":"Global epidemiology of selected sexually transmitted infections","author":"Y Hughes","year":"2022","journal-title":"Sexually Transmissible Oral Diseases. Wiley"},{"issue":"5","key":"pbio.3003297.ref003","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1007\/s00404-012-2240-7","article-title":"Female genital Chlamydia trachomatis infection: where are we heading?","volume":"285","author":"I Mylonas","year":"2012","journal-title":"Arch Gynecol Obstet"},{"key":"pbio.3003297.ref004","first-page":"71","article-title":"The chlamydial developmental cycle.","volume-title":"Micobiology of Chlamydia","author":"ME. Ward","year":"1988"},{"issue":"27","key":"pbio.3003297.ref005","doi-asserted-by":"crossref","first-page":"11430","DOI":"10.1073\/pnas.0703218104","article-title":"Mechanisms of host cell exit by the intracellular bacterium Chlamydia","volume":"104","author":"K Hybiske","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pbio.3003297.ref006","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1046\/j.1462-5822.2000.00029.x","article-title":"A secondary structure motif predictive of protein localization to the chlamydial inclusion membrane","volume":"2","author":"JP Bannantine","year":"2000","journal-title":"Cell Microbiol"},{"key":"pbio.3003297.ref007","doi-asserted-by":"crossref","first-page":"102330","DOI":"10.1016\/j.mib.2023.102330","article-title":"The emerging complexity of Chlamydia trachomatis interactions with host cells as revealed by molecular genetic approaches","volume":"74","author":"RJ Bastidas","year":"2023","journal-title":"Curr Opin Microbiol"},{"issue":"1","key":"pbio.3003297.ref008","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.chom.2016.12.002","article-title":"The Chlamydia trachomatis inclusion membrane protein CpoS counteracts STING-mediated cellular surveillance and suicide programs","volume":"21","author":"BS Sixt","year":"2017","journal-title":"Cell Host Microbe"},{"issue":"7","key":"pbio.3003297.ref009","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1016\/j.celrep.2017.04.058","article-title":"Absence of specific Chlamydia trachomatis inclusion membrane proteins triggers premature inclusion membrane lysis and host cell death","volume":"19","author":"MM Weber","year":"2017","journal-title":"Cell Rep"},{"issue":"12","key":"pbio.3003297.ref010","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2019.02.079","article-title":"Chlamydia trachomatis CT229 subverts Rab GTPase-dependent CCV trafficking pathways to promote chlamydial infection","volume":"26","author":"R Faris","year":"2019","journal-title":"Cell Rep"},{"issue":"4","key":"pbio.3003297.ref011","article-title":"The Chlamydia effector CpoS modulates the inclusion microenvironment and restricts the interferon response by acting on Rab35","volume":"14","author":"K Meier","year":"2023","journal-title":"mBio"},{"issue":"9","key":"pbio.3003297.ref012","doi-asserted-by":"crossref","first-page":"5362","DOI":"10.1128\/IAI.00539-06","article-title":"The GTPase Rab4 interacts with Chlamydia trachomatis inclusion membrane protein CT229","volume":"74","author":"KA Rzomp","year":"2006","journal-title":"Infect Immun"},{"key":"pbio.3003297.ref013","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkz369","article-title":"g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update)","volume":"47","author":"U Raudvere","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"pbio.3003297.ref014","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkab1028","article-title":"The reactome pathway knowledgebase 2022","volume":"50","author":"M Gillespie","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"pbio.3003297.ref015","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: protein\u2013protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"D Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res"},{"issue":"25","key":"pbio.3003297.ref016","doi-asserted-by":"crossref","first-page":"10059","DOI":"10.1073\/pnas.1120244109","article-title":"Attachment of Chlamydia trachomatis L2 to host cells requires sulfation","volume":"109","author":"DM Rosmarin","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pbio.3003297.ref017","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1099\/jmm.0.05497-0","article-title":"Chlorate: a reversible inhibitor of proteoglycan sulphation in Chlamydia trachomatis-infected cells","volume":"53","author":"S Fadel","year":"2004","journal-title":"J Med Microbiol"},{"issue":"23","key":"pbio.3003297.ref018","doi-asserted-by":"crossref","first-page":"5323","DOI":"10.1128\/JB.00780-13","article-title":"Characterization of the interaction between the chlamydial adhesin OmcB and the human host cell","volume":"195","author":"T Fechtner","year":"2013","journal-title":"J Bacteriol"},{"key":"pbio.3003297.ref019","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.isci.2018.12.011","article-title":"A FACS-based genome-wide CRISPR screen reveals a requirement for COPI in Chlamydia trachomatis invasion","volume":"11","author":"JS Park","year":"2019","journal-title":"iScience"},{"issue":"12","key":"pbio.3003297.ref020","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1369\/0022155412464972","article-title":"Heparan sulfate biosynthesis: regulation and variability","volume":"60","author":"J Kreuger","year":"2012","journal-title":"J Histochem Cytochem"},{"key":"pbio.3003297.ref021","doi-asserted-by":"crossref","first-page":"760532","DOI":"10.3389\/fcell.2021.760532","article-title":"Proteoglycans and glycosaminoglycans in stem cell homeostasis and bone tissue regeneration","volume":"9","author":"J Chen","year":"2021","journal-title":"Front Cell Dev Biol"},{"issue":"2","key":"pbio.3003297.ref022","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/glycob\/cwq154","article-title":"Expression and the role of 3\u2032-phosphoadenosine 5\u2032-phosphosulfate transporters in human colorectal carcinoma","volume":"21","author":"S Kamiyama","year":"2011","journal-title":"Glycobiology"},{"issue":"8","key":"pbio.3003297.ref023","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1002\/humu.22104","article-title":"Further delineation of CANT1 phenotypic spectrum and demonstration of its role in proteoglycan synthesis","volume":"33","author":"M Nizon","year":"2012","journal-title":"Hum Mutat"},{"issue":"1","key":"pbio.3003297.ref024","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41419-021-04458-1","article-title":"TMEM165 a new player in proteoglycan synthesis: loss of TMEM165 impairs elongation of chondroitin- and heparan-sulfate glycosaminoglycan chains of proteoglycans and triggers early chondrocyte differentiation and hypertrophy","volume":"13","author":"S Khan","year":"2021","journal-title":"Cell Death Dis"},{"issue":"3","key":"pbio.3003297.ref025","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1128\/JVI.02055-15","article-title":"A haploid genetic screen identifies heparan sulfate proteoglycans supporting rift valley fever virus infection","volume":"90","author":"AM Riblett","year":"2016","journal-title":"J Virol"},{"issue":"1","key":"pbio.3003297.ref026","doi-asserted-by":"crossref","first-page":"3087","DOI":"10.1038\/s41467-018-05191-8","article-title":"SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects","volume":"9","author":"J Dubail","year":"2018","journal-title":"Nat Commun"},{"key":"pbio.3003297.ref027","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.isci.2019.05.005","article-title":"A CRISPR screen using subtilase cytotoxin identifies SLC39A9 as a glycan-regulating factor","volume":"15","author":"T Yamaji","year":"2019","journal-title":"iScience"},{"issue":"10","key":"pbio.3003297.ref028","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1038\/ncb1773","article-title":"GPHR is a novel anion channel critical for acidification and functions of the Golgi apparatus","volume":"10","author":"Y Maeda","year":"2008","journal-title":"Nat Cell Biol"},{"issue":"24","key":"pbio.3003297.ref029","doi-asserted-by":"crossref","first-page":"2890","DOI":"10.15252\/embj.201488375","article-title":"Shedding of glycan-modifying enzymes by signal peptide peptidase-like 3 (SPPL3) regulates cellular N-glycosylation","volume":"33","author":"M Voss","year":"2014","journal-title":"EMBO J"},{"issue":"6","key":"pbio.3003297.ref030","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1074\/mcp.M115.048298","article-title":"Secretome analysis identifies novel signal peptide peptidase-like 3 (Sppl3) substrates and reveals a role of Sppl3 in multiple Golgi glycosylation pathways","volume":"14","author":"P-H Kuhn","year":"2015","journal-title":"Mol Cell Proteomics"},{"issue":"6","key":"pbio.3003297.ref031","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1002\/hep.31218","article-title":"Mutations in the V-ATPase assembly factor VMA21 cause a congenital disorder of glycosylation with autophagic liver disease","volume":"72","author":"M Cannata Serio","year":"2020","journal-title":"Hepatology"},{"issue":"13","key":"pbio.3003297.ref032","doi-asserted-by":"crossref","first-page":"4654","DOI":"10.3390\/ijms21134654","article-title":"Sugary logistics gone wrong: membrane trafficking and congenital disorders of glycosylation","volume":"21","author":"PTA Linders","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"10","key":"pbio.3003297.ref033","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1009996","article-title":"Heparan sulfate proteoglycans serve as alternative receptors for low affinity LCMV variants","volume":"17","author":"A Volland","year":"2021","journal-title":"PLoS Pathog"},{"issue":"8","key":"pbio.3003297.ref034","doi-asserted-by":"crossref","DOI":"10.1083\/jcb.202105004","article-title":"Capture and delivery of tail-anchored proteins to the endoplasmic reticulum","volume":"220","author":"\u00c1 Farkas","year":"2021","journal-title":"J Cell Biol"},{"issue":"7","key":"pbio.3003297.ref035","doi-asserted-by":"crossref","first-page":"6069","DOI":"10.3390\/ijms24076069","article-title":"Role of GARP vesicle tethering complex in Golgi physiology","volume":"24","author":"A Khakurel","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"17","key":"pbio.3003297.ref036","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1002\/1873-3468.13570","article-title":"Maintaining order: COG complex controls Golgi trafficking, processing, and sorting","volume":"593","author":"JB Blackburn","year":"2019","journal-title":"FEBS Lett"},{"issue":"17","key":"pbio.3003297.ref037","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1091\/mbc.E21-04-0169","article-title":"The Golgi-associated retrograde protein (GARP) complex plays an essential role in the maintenance of the Golgi glycosylation machinery","volume":"32","author":"A Khakurel","year":"2021","journal-title":"Mol Biol Cell"},{"issue":"2","key":"pbio.3003297.ref038","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1600-0854.2005.00376.x","article-title":"COG complex-mediated recycling of Golgi glycosyltransferases is essential for normal protein glycosylation","volume":"7","author":"A Shestakova","year":"2006","journal-title":"Traffic"},{"issue":"2","key":"pbio.3003297.ref039","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1128\/IAI.69.2.968-976.2001","article-title":"Infectivity of Chlamydia trachomatis serovar LGV but not E is dependent on host cell heparan sulfate","volume":"69","author":"M Taraktchoglou","year":"2001","journal-title":"Infect Immun"},{"key":"pbio.3003297.ref040","first-page":"20","article-title":"TRAPP complexes in secretion and autophagy","volume":"4","author":"JJ Kim","year":"2016","journal-title":"Front Cell Dev Biol"},{"issue":"8","key":"pbio.3003297.ref041","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nrm2728","article-title":"Rab GTPases as coordinators of vesicle traffic","volume":"10","author":"H Stenmark","year":"2009","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"10","key":"pbio.3003297.ref042","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1111\/j.1600-0854.2012.01397.x","article-title":"TBC1D13 is a RAB35 specific GAP that plays an important role in GLUT4 trafficking in adipocytes","volume":"13","author":"JR Davey","year":"2012","journal-title":"Traffic"},{"issue":"2","key":"pbio.3003297.ref043","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.advms.2023.10.004","article-title":"Ceramides and their roles in programmed cell death","volume":"68","author":"MB Pil\u00e1tov\u00e1","year":"2023","journal-title":"Adv Med Sci"},{"issue":"11","key":"pbio.3003297.ref044","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1080\/15548627.2016.1213927","article-title":"Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilization","volume":"12","author":"S Hern\u00e1ndez-Tiedra","year":"2016","journal-title":"Autophagy"},{"issue":"8","key":"pbio.3003297.ref045","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1194\/jlr.M049759","article-title":"Inhibition of dihydroceramide desaturase activity by the sphingosine kinase inhibitor SKI II","volume":"55","author":"F Cingolani","year":"2014","journal-title":"J Lipid Res"},{"issue":"6","key":"pbio.3003297.ref046","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1046\/j.1462-5822.2000.00077.x","article-title":"Host cell-derived sphingolipids are required for the intracellular growth of Chlamydia trachomatis","volume":"2","author":"C van Ooij","year":"2000","journal-title":"Cell Microbiol"},{"issue":"11","key":"pbio.3003297.ref047","doi-asserted-by":"crossref","first-page":"4877","DOI":"10.1073\/pnas.92.11.4877","article-title":"Lipid metabolism in Chlamydia trachomatis-infected cells: directed trafficking of Golgi-derived sphingolipids to the chlamydial inclusion","volume":"92","author":"T Hackstadt","year":"1995","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"pbio.3003297.ref048","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1002198","article-title":"Chlamydia trachomatis co-opts GBF1 and CERT to acquire host sphingomyelin for distinct roles during intracellular development","volume":"7","author":"CA Elwell","year":"2011","journal-title":"PLoS Pathog"},{"issue":"6","key":"pbio.3003297.ref049","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1002092","article-title":"The lipid transfer protein CERT interacts with the Chlamydia inclusion protein IncD and participates to ER-Chlamydia inclusion membrane contact sites","volume":"7","author":"I Derr\u00e9","year":"2011","journal-title":"PLoS Pathog"},{"issue":"5","key":"pbio.3003297.ref050","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1128\/IAI.01530-14","article-title":"Expression of the effector protein IncD in Chlamydia trachomatis mediates recruitment of the lipid transfer protein CERT and the endoplasmic reticulum-resident protein VAPB to the inclusion membrane","volume":"82","author":"H Agaisse","year":"2014","journal-title":"Infect Immun"},{"issue":"11","key":"pbio.3003297.ref051","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000664","article-title":"Inclusion biogenesis and reactivation of persistent Chlamydia trachomatis requires host cell sphingolipid biosynthesis","volume":"5","author":"DK Robertson","year":"2009","journal-title":"PLoS Pathog"},{"issue":"3","key":"pbio.3003297.ref052","doi-asserted-by":"crossref","first-page":"101","DOI":"10.15698\/mic2017.03.564","article-title":"Chlamydia trachomatis\u2019 struggle to keep its host alive","volume":"4","author":"BS Sixt","year":"2017","journal-title":"Microb Cell"},{"issue":"1","key":"pbio.3003297.ref053","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nbt1044","article-title":"Protein tagging and detection with engineered self-assembling fragments of green fluorescent protein","volume":"23","author":"S Cabantous","year":"2005","journal-title":"Nat Biotechnol"},{"key":"pbio.3003297.ref054","doi-asserted-by":"crossref","DOI":"10.1093\/femspd\/fty011","article-title":"Direct visualization of the expression and localization of chlamydial effector proteins within infected host cells","volume":"76","author":"X Wang","year":"2018","journal-title":"Pathog Dis"},{"issue":"9","key":"pbio.3003297.ref055","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0074768","article-title":"C22:0- and C24:0-dihydroceramides confer mixed cytotoxicity in T-cell acute lymphoblastic leukemia cell lines","volume":"8","author":"Jr Holliday MW","year":"2013","journal-title":"PLoS One"},{"issue":"2","key":"pbio.3003297.ref056","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/tra.12239","article-title":"Sphingolipid metabolism and interorganellar transport: localization of sphingolipid enzymes and lipid transfer proteins","volume":"16","author":"T Yamaji","year":"2015","journal-title":"Traffic"},{"issue":"4","key":"pbio.3003297.ref057","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/path.2440","article-title":"The human protein atlas\u2014a tool for pathology","volume":"216","author":"F Pont\u00e9n","year":"2008","journal-title":"J Pathol"},{"key":"pbio.3003297.ref058","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4419-6741-1_1","article-title":"An overview of sphingolipid metabolism: from synthesis to breakdown","volume":"688","author":"CR Gault","year":"2010","journal-title":"Adv Exp Med Biol"},{"issue":"6","key":"pbio.3003297.ref059","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1111\/mmi.14832","article-title":"Inter-species lateral gene transfer focused on the Chlamydia plasticity zone identifies loci associated with immediate cytotoxicity and inclusion stability","volume":"116","author":"ZE Dimond","year":"2021","journal-title":"Mol Microbiol"},{"issue":"4","key":"pbio.3003297.ref060","article-title":"The Chlamydia trachomatis IncM protein interferes with host cell cytokinesis, centrosome positioning, and Golgi distribution and contributes to the stability of the pathogen-containing vacuole","volume":"91","author":"MP Lu\u00eds","year":"2023","journal-title":"Infect Immun"},{"issue":"2","key":"pbio.3003297.ref061","doi-asserted-by":"crossref","DOI":"10.1128\/msphere.00003-23","article-title":"Homologues of the Chlamydia trachomatis and Chlamydia muridarum inclusion membrane protein IncS are interchangeable for early development but not for inclusion stability in the late developmental cycle","volume":"8","author":"ME Cortina","year":"2023","journal-title":"mSphere"},{"issue":"12","key":"pbio.3003297.ref062","doi-asserted-by":"crossref","DOI":"10.1016\/j.chom.2022.08.008","article-title":"The bacterial effector GarD shields Chlamydia trachomatis inclusions from RNF213-mediated ubiquitylation and destruction","volume":"30","author":"SC Walsh","year":"2022","journal-title":"Cell Host Microbe"},{"issue":"2","key":"pbio.3003297.ref063","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.chom.2008.05.018","article-title":"Actin and intermediate filaments stabilize the Chlamydia trachomatis vacuole by forming dynamic structural scaffolds","volume":"4","author":"Y Kumar","year":"2008","journal-title":"Cell Host Microbe"},{"issue":"1","key":"pbio.3003297.ref064","doi-asserted-by":"crossref","DOI":"10.1128\/spectrum.02614-22","article-title":"Chlamydia trachomatis subverts alpha-actinins to stabilize its inclusion","volume":"11","author":"A Haines","year":"2023","journal-title":"Microbiol Spectr"},{"issue":"4","key":"pbio.3003297.ref065","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/j.1462-5822.2009.01415.x","article-title":"Galectin-3, a marker for vacuole lysis by invasive pathogens","volume":"12","author":"I Paz","year":"2010","journal-title":"Cell Microbiol"},{"issue":"7385","key":"pbio.3003297.ref066","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/nature10744","article-title":"Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion","volume":"482","author":"TLM Thurston","year":"2012","journal-title":"Nature"},{"issue":"15","key":"pbio.3003297.ref067","doi-asserted-by":"crossref","first-page":"2974","DOI":"10.1016\/j.cub.2020.05.083","article-title":"Transbilayer movement of sphingomyelin precedes catastrophic breakage of enterobacteria-containing vacuoles","volume":"30","author":"CJ Ellison","year":"2020","journal-title":"Curr Biol"},{"key":"pbio.3003297.ref068","first-page":"4883","article-title":"The ubiquitin-like modifier FAT10 decorates autophagy-targeted Salmonella and contributes to Salmonella resistance in mice","volume":"127","author":"V Spinnenhirn","year":"2014","journal-title":"J Cell Sci"},{"issue":"7500","key":"pbio.3003297.ref069","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/nature13157","article-title":"Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN-induced GTPases","volume":"509","author":"E Meunier","year":"2014","journal-title":"Nature"},{"issue":"2","key":"pbio.3003297.ref070","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00385-19","article-title":"Genetic screen in Chlamydia muridarum reveals role for an interferon-induced host cell death program in antimicrobial inclusion rupture","volume":"10","author":"AM Giebel","year":"2019","journal-title":"mBio"},{"key":"pbio.3003297.ref071","doi-asserted-by":"crossref","first-page":"14729","DOI":"10.1038\/ncomms14729","article-title":"Laser-mediated rupture of chlamydial inclusions triggers pathogen egress and host cell necrosis","volume":"8","author":"MC Kerr","year":"2017","journal-title":"Nat Commun"},{"issue":"5","key":"pbio.3003297.ref072","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.03981-24","article-title":"Chlamydia trachomatis exploits sphingolipid metabolic pathways during infection of phagocytes","volume":"16","author":"A Moldovan","year":"2025","journal-title":"mBio"},{"issue":"12","key":"pbio.3003297.ref073","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1091\/mbc.e12-11-0827","article-title":"Toxoplasma gondii salvages sphingolipids from the host Golgi through the rerouting of selected Rab vesicles to the parasitophorous vacuole","volume":"24","author":"JD Romano","year":"2013","journal-title":"Mol Biol Cell"},{"key":"pbio.3003297.ref074","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.mib.2020.01.008","article-title":"The vacuole guard hypothesis: how intravacuolar pathogens fight to maintain the integrity of their beloved home","volume":"54","author":"I Anand","year":"2020","journal-title":"Curr Opin Microbiol"},{"issue":"13","key":"pbio.3003297.ref075","doi-asserted-by":"crossref","first-page":"3235","DOI":"10.1093\/emboj\/19.13.3235","article-title":"Salmonella maintains the integrity of its intracellular vacuole through the action of SifA","volume":"19","author":"CR Beuz\u00f3n","year":"2000","journal-title":"EMBO J"},{"issue":"9","key":"pbio.3003297.ref076","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1073\/pnas.1121286109","article-title":"The protein SdhA maintains the integrity of the Legionella-containing vacuole","volume":"109","author":"EA Creasey","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pbio.3003297.ref077","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.mib.2013.11.005","article-title":"Maintenance of vacuole integrity by bacterial pathogens","volume":"17","author":"EA Creasey","year":"2014","journal-title":"Curr Opin Microbiol"},{"issue":"2","key":"pbio.3003297.ref078","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1002507","article-title":"Phagosomal rupture by Mycobacterium tuberculosis results in toxicity and host cell death","volume":"8","author":"R Simeone","year":"2012","journal-title":"PLoS Pathog"},{"issue":"3","key":"pbio.3003297.ref079","doi-asserted-by":"crossref","first-page":"156","DOI":"10.4161\/auto.2825","article-title":"Autophagy recognizes intracellular Salmonella enterica serovar Typhimurium in damaged vacuoles","volume":"2","author":"CL Birmingham","year":"2006","journal-title":"Autophagy"},{"issue":"6122","key":"pbio.3003297.ref080","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1126\/science.1230751","article-title":"Caspase-11 protects against bacteria that escape the vacuole","volume":"339","author":"Y Aachoui","year":"2013","journal-title":"Science"},{"issue":"11","key":"pbio.3003297.ref081","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000665","article-title":"Identification of host cytosolic sensors and bacterial factors regulating the type I interferon response to Legionella pneumophila","volume":"5","author":"KM Monroe","year":"2009","journal-title":"PLoS Pathog"},{"issue":"2","key":"pbio.3003297.ref082","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nbt.3437","article-title":"Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9","volume":"34","author":"JG Doench","year":"2016","journal-title":"Nat Biotechnol"},{"key":"pbio.3003297.ref083","doi-asserted-by":"crossref","first-page":"31782","DOI":"10.1038\/srep31782","article-title":"Increasing the performance of pooled CRISPR-Cas9 drop-out screening","volume":"6","author":"BCS Cross","year":"2016","journal-title":"Sci Rep"},{"issue":"10","key":"pbio.3003297.ref084","doi-asserted-by":"crossref","first-page":"945","DOI":"10.15252\/msb.20177834","article-title":"CRISPR\/Cas9 screening using unique molecular identifiers","volume":"13","author":"B Schmierer","year":"2017","journal-title":"Mol Syst Biol"},{"issue":"12","key":"pbio.3003297.ref085","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1186\/s13059-014-0554-4","article-title":"MAGeCK enables robust identification of essential genes from genome-scale CRISPR\/Cas9 knockout screens","volume":"15","author":"W Li","year":"2014","journal-title":"Genome Biol"},{"issue":"9","key":"pbio.3003297.ref086","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1002258","article-title":"Development of a transformation system for Chlamydia trachomatis: restoration of glycogen biosynthesis by acquisition of a plasmid shuttle vector","volume":"7","author":"Y Wang","year":"2011","journal-title":"PLoS Pathog"},{"issue":"12","key":"pbio.3003297.ref087","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1038\/s41380-018-0090-9","article-title":"Antidepressants act by inducing autophagy controlled by sphingomyelin-ceramide","volume":"23","author":"A Gulbins","year":"2018","journal-title":"Mol Psychiatry"},{"issue":"6","key":"pbio.3003297.ref088","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1194\/jlr.RA120000682","article-title":"Characterization of the small molecule ARC39, a direct and specific inhibitor of acid sphingomyelinase in vitro","volume":"61","author":"E Naser","year":"2020","journal-title":"J Lipid Res"},{"issue":"2","key":"pbio.3003297.ref089","article-title":"The Chlamydia trachomatis type III secretion chaperone Slc1 engages multiple early effectors, including TepP, a tyrosine-phosphorylated protein required for the recruitment of CrkI-II to nascent inclusions and innate immune signaling","volume":"10","author":"Y-S Chen","year":"2014","journal-title":"PLoS Pathog"},{"issue":"1","key":"pbio.3003297.ref090","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1186\/s12859-021-04344-9","article-title":"CellProfiler 4: improvements in speed, utility and usability","volume":"22","author":"DR Stirling","year":"2021","journal-title":"BMC Bioinformatics"},{"key":"pbio.3003297.ref091","volume-title":"NCMIR methods for 3D EM: a new protocol for preparation of biological specimens for serial block face scanning electron microscopy","author":"TJ Deerinck","year":"2010"},{"issue":"11","key":"pbio.3003297.ref092","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"P Shannon","year":"2003","journal-title":"Genome Res"},{"issue":"11","key":"pbio.3003297.ref093","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0013984","article-title":"Enrichment map: a network-based method for gene-set enrichment visualization and interpretation","volume":"5","author":"D Merico","year":"2010","journal-title":"PLoS One"}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003297","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T17:22:11Z","timestamp":1755019331000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003297"}},"subtitle":[],"editor":[{"given":"Ken","family":"Cadwell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,8,12]]},"references-count":93,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.3003297","relation":{},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,12]]}}}