{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:15:00Z","timestamp":1790734500901,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010184","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T00:00:00Z","timestamp":1641772800000}}],"reference-count":112,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T00:00:00Z","timestamp":1640649600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012612","name":"lsu health shreveport","doi-asserted-by":"publisher","award":["Start up funds"],"award-info":[{"award-number":["Start up funds"]}],"id":[{"id":"10.13039\/100012612","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012612","name":"lsu health shreveport","doi-asserted-by":"publisher","award":["Start up funds"],"award-info":[{"award-number":["Start up funds"]}],"id":[{"id":"10.13039\/100012612","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"national institute of general medical sciences","doi-asserted-by":"publisher","award":["P20GM134974"],"award-info":[{"award-number":["P20GM134974"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"national institute of general medical sciences","doi-asserted-by":"publisher","award":["U54 GM104940"],"award-info":[{"award-number":["U54 GM104940"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Dynamic reorganization of the actin cytoskeleton dictates plasma membrane morphogenesis and is frequently subverted by bacterial pathogens for entry and colonization of host cells. The human-adapted bacterial pathogen\n                    <jats:italic>Neisseria gonorrhoeae<\/jats:italic>\n                    can colonize and replicate when cultured with human macrophages, however the basic understanding of how this process occurs is incomplete.\n                    <jats:italic>N<\/jats:italic>\n                    .\n                    <jats:italic>gonorrhoeae<\/jats:italic>\n                    is the etiological agent of the sexually transmitted disease gonorrhea and tissue resident macrophages are present in the urogenital mucosa, which is colonized by the bacteria. We uncovered that when gonococci colonize macrophages, they can establish an intracellular or a cell surface-associated niche that support bacterial replication independently. Unlike other intracellular bacterial pathogens, which enter host cells as single bacterium, establish an intracellular niche and then replicate, gonococci invade human macrophages as a colony. Individual diplococci are rapidly phagocytosed by macrophages and transported to lysosomes for degradation. However, we found that surface-associated gonococcal colonies of various sizes can invade macrophages by triggering actin skeleton rearrangement resulting in plasma membrane invaginations that slowly engulf the colony. The resulting intracellular membrane-bound organelle supports robust bacterial replication. The gonococci-occupied vacuoles evaded fusion with the endosomal compartment and were enveloped by a network of actin filaments. We demonstrate that gonococcal colonies invade macrophages via a process mechanistically distinct from phagocytosis that is regulated by the actin nucleating factor FMNL3 and is independent of the Arp2\/3 complex. Our work provides insights into the gonococci life-cycle in association with human macrophages and defines key host determinants for macrophage colonization.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010184","type":"journal-article","created":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T14:51:34Z","timestamp":1640703094000},"page":"e1010184","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Neisseria gonorrhoeae subverts formin-dependent actin polymerization to colonize human macrophages"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3294-7595","authenticated-orcid":true,"given":"Stanimir 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Dwindling Treatment Options","volume":"379","author":"S Blank","year":"2018","journal-title":"N Engl J Med"},{"issue":"4","key":"ppat.1010184.ref002","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/nrmicro.2017.169","article-title":"Neisseria gonorrhoeae host adaptation and pathogenesis","volume":"16","author":"SJ Quillin","year":"2018","journal-title":"Nat Rev Microbiol"},{"issue":"3","key":"ppat.1010184.ref003","doi-asserted-by":"crossref","first-page":"e009629","DOI":"10.1136\/bmjopen-2015-009629","article-title":"Analysis of the sex ratio of reported gonorrhoea incidence in Shenzhen, China.","volume":"6","author":"M Xiong","year":"2016","journal-title":"BMJ Open"},{"issue":"5","key":"ppat.1010184.ref004","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/j.1600-0897.1997.tb00311.x","article-title":"Flow cytometric analysis of leukocytes in the human female reproductive tract: comparison of fallopian tube, uterus, cervix, and 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X. Pili and leukocyte association factor as mediators of interactions between gonococci and eukaryotic cells in vitro","volume":"11","author":"J Swanson","year":"1975","journal-title":"Infection and immunity"},{"issue":"3","key":"ppat.1010184.ref033","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1046\/j.1365-2958.1999.01230.x","article-title":"Mutagenesis of the Neisseria gonorrhoeae porin reduces invasion in epithelial cells and enhances phagocyte responsiveness","volume":"31","author":"FJ Bauer","year":"1999","journal-title":"Molecular microbiology"},{"issue":"6","key":"ppat.1010184.ref034","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.chom.2007.11.002","article-title":"Host glycoprotein Gp96 and scavenger receptor SREC interact with PorB of disseminating Neisseria gonorrhoeae in an epithelial invasion pathway","volume":"2","author":"C Rechner","year":"2007","journal-title":"Cell host & 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cells and neutrophils are receptors for Opa proteins of pathogenic neisseriae.","volume":"22","author":"M Virji","year":"1996","journal-title":"Molecular microbiology"},{"issue":"13","key":"ppat.1010184.ref046","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1128\/JB.00171-13","article-title":"Constitutively Opa-expressing and Opa-deficient neisseria gonorrhoeae strains differentially stimulate and survive exposure to human neutrophils","volume":"195","author":"LM Ball","year":"2013","journal-title":"Journal of bacteriology"},{"issue":"9","key":"ppat.1010184.ref047","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1111\/j.1462-5822.2007.00947.x","article-title":"The specific innate immune receptor CEACAM3 triggers neutrophil bactericidal activities via a Syk kinase-dependent pathway","volume":"9","author":"H Sarantis","year":"2007","journal-title":"Cell 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Z\u00f6llner","year":"2017","journal-title":"Scientific reports"},{"issue":"23","key":"ppat.1010184.ref051","doi-asserted-by":"crossref","first-page":"6468","DOI":"10.1128\/JB.00969-12","article-title":"Construction and characterization of a derivative of Neisseria gonorrhoeae strain MS11 devoid of all opa genes","volume":"194","author":"A LeVan","year":"2012","journal-title":"Journal of bacteriology"},{"issue":"Pt 6","key":"ppat.1010184.ref052","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1242\/jcs.115.6.1231","article-title":"Microvilli-like structures are associated with the internalization of virulent capsulated Neisseria meningitidis into vascular endothelial cells","volume":"115","author":"E Eugene","year":"2002","journal-title":"Journal of cell science"},{"issue":"10","key":"ppat.1010184.ref053","doi-asserted-by":"crossref","first-page":"4743","DOI":"10.1128\/IAI.00687-07","article-title":"Dynamics of Neisseria gonorrhoeae attachment: microcolony development, 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Dumenil","year":"2011","journal-title":"Cell Microbiol"},{"issue":"4","key":"ppat.1010184.ref058","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1128\/IAI.74.4.2428-2435.2006","article-title":"Monoclonal antibody detection of CD46 clustering beneath Neisseria gonorrhoeae microcolonies","volume":"74","author":"NJ Weyand","year":"2006","journal-title":"Infection and immunity"},{"issue":"2","key":"ppat.1010184.ref059","doi-asserted-by":"crossref","first-page":"e1000314","DOI":"10.1371\/journal.ppat.1000314","article-title":"Extracellular bacterial pathogen induces host cell surface reorganization to resist shear stress","volume":"5","author":"G Mikaty","year":"2009","journal-title":"PLoS pathogens"},{"issue":"12","key":"ppat.1010184.ref060","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1016\/j.tim.2018.07.003","article-title":"Gonococcal Defenses against Antimicrobial Activities of Neutrophils","volume":"26","author":"A Palmer","year":"2018","journal-title":"Trends Microbiol"},{"issue":"2","key":"ppat.1010184.ref061","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1099\/00221287-113-2-395","article-title":"Demonstration of intracellular growth of gonococci in human phagocytes using spectinomycin to kill extracellular organisms","volume":"113","author":"SG Casey","year":"1979","journal-title":"Journal of general microbiology"},{"issue":"2","key":"ppat.1010184.ref062","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1099\/00221287-113-2-383","article-title":"The intracellular survival and growth of gonococci in human phagocytes","volume":"113","author":"DR Veale","year":"1979","journal-title":"Journal of general microbiology"},{"issue":"1","key":"ppat.1010184.ref063","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1083\/jcb.201103148","article-title":"Pathogens and polymers: microbe-host interactions illuminate the cytoskeleton","volume":"195","author":"CM Haglund","year":"2011","journal-title":"The Journal of cell biology"},{"issue":"7","key":"ppat.1010184.ref064","first-page":"687","article-title":"Bacterial subversion of host cytoskeletal machinery: hijacking formins and the Arp2\/3 complex. BioEssays: news and reviews in molecular","volume":"36","author":"D Truong","year":"2014","journal-title":"cellular and developmental biology"},{"issue":"Pt 8","key":"ppat.1010184.ref065","first-page":"1855","article-title":"Actin stress fibers\u2014assembly, dynamics and biological roles","volume":"125","author":"S Tojkander","year":"2012","journal-title":"Journal of cell science"},{"issue":"1","key":"ppat.1010184.ref066","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1471-2164-5-23","article-title":"Microarray genomotyping of key experimental strains of Neisseria gonorrhoeae reveals gene complement diversity and five new neisserial genes associated with Minimal Mobile Elements","volume":"5","author":"LA Snyder","year":"2004","journal-title":"BMC genomics"},{"issue":"6","key":"ppat.1010184.ref067","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1128\/iai.62.6.2222-2228.1994","article-title":"Gentamicin kills intracellular Listeria monocytogenes","volume":"62","author":"DA Drevets","year":"1994","journal-title":"Infection and immunity"},{"issue":"4","key":"ppat.1010184.ref068","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":"ppat.1010184.ref069","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":"TL Thurston","year":"2012","journal-title":"Nature"},{"key":"ppat.1010184.ref070","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ceb.2020.05.011","article-title":"A mechanical perspective on phagocytic cup formation","volume":"66","author":"D Vorselen","year":"2020","journal-title":"Current opinion in cell biology"},{"issue":"1","key":"ppat.1010184.ref071","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/imr.12439","article-title":"The life cycle of phagosomes: formation, maturation, and resolution","volume":"273","author":"R Levin","year":"2016","journal-title":"Immunological reviews"},{"issue":"5","key":"ppat.1010184.ref072","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/j.bpj.2013.07.036","article-title":"Phagocytosis dynamics depends on target shape","volume":"105","author":"D Paul","year":"2013","journal-title":"Biophys J"},{"key":"ppat.1010184.ref073","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/1752-0509-4-149","article-title":"The zipper mechanism in phagocytosis: energetic requirements and variability in phagocytic cup shape","volume":"4","author":"S Tollis","year":"2010","journal-title":"BMC Syst Biol"},{"issue":"3","key":"ppat.1010184.ref074","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1046\/j.1365-2958.1998.00841.x","article-title":"Legionella pneumophila DotA protein is required for early phagosome trafficking decisions that occur within minutes of bacterial uptake","volume":"28","author":"CR Roy","year":"1998","journal-title":"Molecular microbiology"},{"issue":"1","key":"ppat.1010184.ref075","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/imr.12212","article-title":"Phagocytosis: receptors, signal integration, and the cytoskeleton","volume":"262","author":"SA Freeman","year":"2014","journal-title":"Immunological reviews"},{"issue":"7","key":"ppat.1010184.ref076","doi-asserted-by":"crossref","first-page":"5241","DOI":"10.1016\/S0021-9258(17)37680-9","article-title":"A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002).","volume":"269","author":"CJ Vlahos","year":"1994","journal-title":"The Journal of biological chemistry"},{"issue":"6","key":"ppat.1010184.ref077","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.devcel.2006.04.002","article-title":"Dynasore, a cell-permeable inhibitor of dynamin","volume":"10","author":"E Macia","year":"2006","journal-title":"Dev Cell"},{"issue":"11","key":"ppat.1010184.ref078","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.chembiol.2009.10.006","article-title":"Identification and characterization of a small molecule inhibitor of formin-mediated actin assembly","volume":"16","author":"SA Rizvi","year":"2009","journal-title":"Chem Biol"},{"issue":"5","key":"ppat.1010184.ref079","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.chembiol.2013.03.019","article-title":"Small molecules CK-666 and CK-869 inhibit actin-related protein 2\/3 complex by blocking an activating conformational change","volume":"20","author":"B Hetrick","year":"2013","journal-title":"Chem Biol"},{"key":"ppat.1010184.ref080","first-page":"132","article-title":"LC3-associated phagocytosis at a glance","author":"BL Heckmann","year":"2019","journal-title":"Journal of cell science"},{"key":"ppat.1010184.ref081","first-page":"126","article-title":"Formins at a glance","author":"D Breitsprecher","year":"2013","journal-title":"Journal of cell science"},{"issue":"5","key":"ppat.1010184.ref082","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1111\/j.1365-2958.1994.tb00483.x","article-title":"The opaH locus of Neisseria gonorrhoeae MS11A is involved in epithelial cell invasion","volume":"13","author":"LS Waldbeser","year":"1994","journal-title":"Molecular microbiology"},{"issue":"2","key":"ppat.1010184.ref083","doi-asserted-by":"crossref","first-page":"e56705","DOI":"10.1371\/journal.pone.0056705","article-title":"with dendritic cells suppresses their ability to elicit an HIV-1-specific T cell memory response","volume":"8","author":"Q Yu","year":"2013","journal-title":"PLoS One"},{"issue":"5581","key":"ppat.1010184.ref084","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1126\/science.1072309","article-title":"Role of formins in actin assembly: nucleation and barbed-end association.","volume":"297","author":"D Pruyne","year":"2002","journal-title":"Science (New York, NY)"},{"issue":"21","key":"ppat.1010184.ref085","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.220814","article-title":"Roles for Ena\/VASP proteins in FMNL3-mediated filopodial assembly","volume":"131","author":"LE Young","year":"2018","journal-title":"Journal of cell science"},{"issue":"8","key":"ppat.1010184.ref086","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.253708","article-title":"The formin inhibitor SMIFH2 inhibits members of the myosin superfamily","volume":"134","author":"Y Nishimura","year":"2021","journal-title":"Journal of cell science"},{"issue":"2","key":"ppat.1010184.ref087","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.bbamcr.2010.01.014","article-title":"Fifteen formins for an actin filament: a molecular view on the regulation of human formins","volume":"1803","author":"A Sch\u00f6nichen","year":"2010","journal-title":"Biochimica et biophysica acta"},{"issue":"8","key":"ppat.1010184.ref088","doi-asserted-by":"crossref","first-page":"5084","DOI":"10.1074\/jbc.M509226200","article-title":"Biochemical characterization of the diaphanous autoregulatory interaction in the formin homology protein FHOD1","volume":"281","author":"A Sch\u00f6nichen","year":"2006","journal-title":"The Journal of biological chemistry"},{"issue":"9","key":"ppat.1010184.ref089","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1016\/j.str.2008.06.008","article-title":"The human formin FHOD1 contains a bipartite structure of FH3 and GTPase-binding domains required for activation","volume":"16","author":"A Schulte","year":"2008","journal-title":"Structure (London, England: 1993)."},{"issue":"7041","key":"ppat.1010184.ref090","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nature03604","article-title":"Structural and mechanistic insights into the interaction between Rho and mammalian Dia","volume":"435","author":"R Rose","year":"2005","journal-title":"Nature"},{"issue":"50","key":"ppat.1010184.ref091","doi-asserted-by":"crossref","first-page":"35236","DOI":"10.1074\/jbc.M805634200","article-title":"Specificity of interactions between mDia isoforms and Rho proteins","volume":"283","author":"M Lammers","year":"2008","journal-title":"The Journal of biological chemistry"},{"issue":"4","key":"ppat.1010184.ref092","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/emboj.2008.7","article-title":"The mammalian formin FHOD1 is activated through phosphorylation by ROCK and mediates thrombin-induced stress fibre formation in endothelial cells","volume":"27","author":"R Takeya","year":"2008","journal-title":"The EMBO journal"},{"issue":"23","key":"ppat.1010184.ref093","doi-asserted-by":"crossref","first-page":"4176","DOI":"10.1038\/sj.emboj.7600879","article-title":"The regulation of mDia1 by autoinhibition and its release by Rho*GTP","volume":"24","author":"M Lammers","year":"2005","journal-title":"The EMBO journal"},{"key":"ppat.1010184.ref094","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.mib.2016.11.007","article-title":"Actin-based motility and cell-to-cell spread of bacterial pathogens","volume":"35","author":"RL Lamason","year":"2017","journal-title":"Current opinion in microbiology"},{"key":"ppat.1010184.ref095","first-page":"175","article-title":"Type III Secreted Virulence Factors Manipulating Signaling to Actin Dynamics","volume":"399","author":"TE Stradal","year":"2017","journal-title":"Current topics in microbiology and immunology"},{"issue":"5","key":"ppat.1010184.ref096","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/S0092-8674(00)81442-7","article-title":"S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells","volume":"93","author":"WD Hardt","year":"1998","journal-title":"Cell"},{"issue":"2","key":"ppat.1010184.ref097","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1111\/j.1574-6976.2006.00013.x","article-title":"Protein secretion and secreted proteins in pathogenic Neisseriaceae","volume":"30","author":"P van Ulsen","year":"2006","journal-title":"FEMS microbiology reviews"},{"key":"ppat.1010184.ref098","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3389\/fmicb.2011.00061","article-title":"The Gonococcal Genetic Island and Type IV Secretion in the Pathogenic Neisseria.","volume":"2","author":"ME Ramsey","year":"2011","journal-title":"Frontiers in microbiology"},{"issue":"1","key":"ppat.1010184.ref099","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1128\/IAI.05702-11","article-title":"Defining the roles of human carcinoembryonic antigen-related cellular adhesion molecules during neutrophil responses to Neisseria gonorrhoeae","volume":"80","author":"H Sarantis","year":"2012","journal-title":"Infection and immunity"},{"key":"ppat.1010184.ref100","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/1471-2180-10-117","article-title":"CEACAM1 recognition by bacterial pathogens is species-specific","volume":"10","author":"M Voges","year":"2010","journal-title":"BMC microbiology"},{"issue":"5","key":"ppat.1010184.ref101","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1128\/IAI.01411-12","article-title":"The formins FMNL1 and mDia1 regulate coiling phagocytosis of Borrelia burgdorferi by primary human macrophages","volume":"81","author":"X Naj","year":"2013","journal-title":"Infection and immunity"},{"issue":"5","key":"ppat.1010184.ref102","doi-asserted-by":"crossref","first-page":"e1005603","DOI":"10.1371\/journal.ppat.1005603","article-title":"Endothelial Cells Use a Formin-Dependent Phagocytosis-Like Process to Internalize the Bacterium Listeria monocytogenes.","volume":"12","author":"M Rengarajan","year":"2016","journal-title":"PLoS pathogens"},{"key":"ppat.1010184.ref103","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.3389\/fimmu.2017.01483","article-title":"Macrophage Autophagy and Bacterial Infections.","volume":"8","author":"A Bah","year":"2017","journal-title":"Frontiers in immunology"},{"key":"ppat.1010184.ref104","first-page":"2471215","article-title":"Autophagy, and Cell Death: The Trinity of Innate Host Defense against Intracellular Bacteria","volume":"2019","author":"Krakauer T. Inflammasomes","year":"2019","journal-title":"Mediators of inflammation"},{"issue":"3","key":"ppat.1010184.ref105","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/nri.2016.147","article-title":"Programmed cell death as a defence against infection","volume":"17","author":"I Jorgensen","year":"2017","journal-title":"Nature reviews Immunology"},{"issue":"1","key":"ppat.1010184.ref106","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/cr.2009.139","article-title":"Complement and its role in innate and adaptive immune responses","volume":"20","author":"JR Dunkelberger","year":"2010","journal-title":"Cell research"},{"key":"ppat.1010184.ref107","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1128\/jb.85.6.1274-1279.1963","article-title":"NEISSERIA GONORRHOEAE. I. VIRULENCE GENETICALLY LINKED TO CLONAL VARIATION","volume":"85","author":"DS, Jr. Kellogg","year":"1963","journal-title":"Journal of bacteriology"},{"issue":"4","key":"ppat.1010184.ref108","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1128\/jcm.10.4.437-441.1979","article-title":"Charcoal-yeast extract agar: primary isolation medium for Legionella pneumophila","volume":"10","author":"JC Feeley","year":"1979","journal-title":"Journal of clinical microbiology"},{"issue":"12","key":"ppat.1010184.ref109","doi-asserted-by":"crossref","first-page":"e1006088","DOI":"10.1371\/journal.ppat.1006088","article-title":"MTOR-Driven Metabolic Reprogramming Regulates Legionella pneumophila Intracellular Niche Homeostasis.","volume":"12","author":"CF Abshire","year":"2016","journal-title":"PLoS pathogens"},{"issue":"8","key":"ppat.1010184.ref110","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/nmeth.3047","article-title":"Improved vectors and genome-wide libraries for CRISPR screening","volume":"11","author":"NE Sanjana","year":"2014","journal-title":"Nature methods"},{"issue":"11","key":"ppat.1010184.ref111","doi-asserted-by":"crossref","first-page":"4447","DOI":"10.1128\/IAI.02078-14","article-title":"The serine\/threonine kinase STK11 promotes Shigella flexneri dissemination through establishment of cell-cell contacts competent for tyrosine kinase signaling","volume":"82","author":"AM Dragoi","year":"2014","journal-title":"Infection and immunity"},{"issue":"6472","key":"ppat.1010184.ref112","doi-asserted-by":"crossref","DOI":"10.1126\/science.aax9198","article-title":"A genome-wide transcriptomic analysis of protein-coding genes in human blood cells","volume":"366","author":"M Uhlen","year":"2019","journal-title":"Science (New York, NY)."}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1010184","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T00:00:00Z","timestamp":1641772800000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010184","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T13:33:30Z","timestamp":1641821610000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010184"}},"subtitle":[],"editor":[{"given":"Ann","family":"Jerse","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,12,28]]},"references-count":112,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1010184","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.01.19.427361","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,28]]}}}