{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:02:01Z","timestamp":1791302521564,"version":"4.1.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Bacteriol."],"published-print":{"date-parts":[[2015,2,1]]},"abstract":"<jats:p><jats:named-content content-type=\"genus-species\">Legionella pneumophila<\/jats:named-content>is a Gram-negative pathogen found mainly in water, either in a free-living form or within infected protozoans, where it replicates. This bacterium can also infect humans by inhalation of contaminated aerosols, causing a severe form of pneumonia called legionellosis or Legionnaires' disease. The involvement of type II and IV secretion systems in the virulence of<jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>is now well documented. Despite bioinformatic studies showing that a type I secretion system (T1SS) could be present in this pathogen, the functionality of this system based on the LssB, LssD, and TolC proteins has never been established. Here, we report the demonstration of the functionality of the T1SS, as well as its role in the infectious cycle of<jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>. Using deletion mutants and fusion proteins, we demonstrated that the<jats:underline>r<\/jats:underline>epeats-in-<jats:underline>t<\/jats:underline>o<jats:underline>x<\/jats:underline>in protein RtxA is secreted through an LssB-LssD-TolC-dependent mechanism. Moreover, fluorescence monitoring and confocal microscopy showed that this T1SS is required for entry into the host cell, although it seems dispensable to the intracellular cycle. Together, these results underline the active participation of<jats:named-content content-type=\"genus-species\">L. pneumophila<\/jats:named-content>, via its T1SS, in its internalization into host cells.<\/jats:p>","DOI":"10.1128\/jb.02164-14","type":"journal-article","created":{"date-parts":[[2014,11,25]],"date-time":"2014-11-25T03:27:05Z","timestamp":1416886025000},"page":"563-571","source":"Crossref","is-referenced-by-count":59,"title":["Functional Type 1 Secretion System Involved in Legionella pneumophila Virulence"],"prefix":"10.1128","volume":"197","author":[{"given":"Fabien","family":"Fuche","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Vianney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Andrea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Doublet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Gilbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2014,11,24]]},"reference":[{"key":"key20180919081436_B1","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1202\/0002-8894(2000)061<0738:ROLD>2.0.CO;2","article-title":"Review of Legionnaires' disease","volume":"61","year":"2000","journal-title":"AIHAJ"},{"key":"key20180919081436_B2","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1002\/jhm.95","article-title":"Community-acquired pneumonia: a practical approach to management for the hospitalist","volume":"1","year":"2006","journal-title":"J Hosp Med"},{"key":"key20180919081436_B3","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1086\/518754","article-title":"Role of environmental surveillance in determining the risk of hospital-acquired legionellosis: a national surveillance study with clinical correlations","volume":"28","year":"2007","journal-title":"Infect Control Hosp Epidemiol"},{"key":"key20180919081436_B4","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1128\/CMR.15.3.506-526.2002","article-title":"Legionella and Legionnaires' disease: 25 years of investigation","volume":"15","year":"2002","journal-title":"Clin Microbiol Rev"},{"key":"key20180919081436_B5","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.micinf.2012.11.001","article-title":"Cell biology of infection by Legionella pneumophila","volume":"15","year":"2013","journal-title":"Microbes Infect"},{"key":"key20180919081436_B6","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1186\/1471-2180-9-S1-S2","article-title":"Protein secretion systems in bacterial-host associations, and their description in the Gene Ontology","volume":"9","year":"2009","journal-title":"BMC Microbiol"},{"key":"key20180919081436_B7","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1128\/IAI.66.4.1776-1782.1998","article-title":"Identification and temperature regulation of Legionella pneumophila genes involved in type IV pilus biogenesis and type II protein secretion","volume":"66","year":"1998","journal-title":"Infect Immun"},{"key":"key20180919081436_B8","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1111\/j.1365-2958.1994.tb01317.x","article-title":"Altered intracellular targeting properties associated with mutations in the Legionella-pneumophila dotA gene","volume":"14","year":"1994","journal-title":"Mol Microbiol"},{"key":"key20180919081436_B9","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1111\/j.1365-2958.1994.tb01316.x","article-title":"The Legionella-pneumophila-icm locus\u2014a set of genes required for intracellular multiplication in human macrophages","volume":"14","year":"1994","journal-title":"Mol Microbiol"},{"key":"key20180919081436_B10","doi-asserted-by":"publisher","first-page":"136","DOI":"10.3389\/fmicb.2011.00136","article-title":"Type IVB secretion systems of Legionella and other Gram-negative bacteria","volume":"2","year":"2011","journal-title":"Front Microbiol"},{"key":"key20180919081436_B11","doi-asserted-by":"publisher","first-page":"3468","DOI":"10.1128\/JB.00430-13","article-title":"Implication of the VirD4 coupling protein of the Lvh type 4 secretion system in virulence phenotypes of Legionella pneumophila","volume":"195","year":"2013","journal-title":"J Bacteriol"},{"issue":"3","key":"key20180919081436_B12","doi-asserted-by":"publisher","first-page":"e17638","DOI":"10.1371\/journal.pone.0017638","article-title":"Comprehensive identification of protein substrates of the Dot\/Icm type IV transporter of Legionella pneumophila","volume":"6","year":"2011","journal-title":"PLoS One"},{"key":"key20180919081436_B13","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1016\/j.micinf.2013.09.007","article-title":"Molecular mimicry and original biochemical strategies for the biogenesis of a Legionella pneumophila replicative niche in phagocytic cells","volume":"15","year":"2013","journal-title":"Microbes Infect"},{"key":"key20180919081436_B14","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1078\/1438-4221-00276","article-title":"Description of a putative type I secretion system in Legionella pneumophila","volume":"293","year":"2003","journal-title":"Int J Med Microbiol"},{"key":"key20180919081436_B15","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1099\/00222615-13-1-57","article-title":"Uropathogenic properties of Escherichia-coli in recurrent urinary-tract infection","volume":"13","year":"1980","journal-title":"J Med Microbiol"},{"key":"key20180919081436_B16","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.mib.2009.01.001","article-title":"Virulence factor secretion and translocation by Bordetella species","volume":"12","year":"2009","journal-title":"Curr Opin Microbiol"},{"key":"key20180919081436_B17","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1099\/mic.0.26171-0","article-title":"Genetic and biochemical characterization of PrtA, an RTX-like metalloprotease from Photorhabdus","volume":"149","year":"2003","journal-title":"Microbiology"},{"key":"key20180919081436_B18","first-page":"159","article-title":"Secretion of hemolysin by Escherichia coli","volume":"125","year":"1986","journal-title":"Curr Top Microbiol Immunol"},{"key":"key20180919081436_B19","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/0300-9084(90)90140-C","article-title":"Secretion of extracellular proteins by Pseudomonas aeruginosa","volume":"72","year":"1990","journal-title":"Biochimie"},{"key":"key20180919081436_B20","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1002\/j.1460-2075.1990.tb08252.x","article-title":"Protease secretion by Erwinia chrysanthemi\u2014the specific secretion functions are analogous to those of Escherichia coli alpha-hemolysin","volume":"9","year":"1990","journal-title":"EMBO J"},{"key":"key20180919081436_B21","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1146\/annurev.biochem.73.011303.074104","article-title":"Structure and function of tolC: The bacterial exit duct for proteins and drugs","volume":"73","year":"2004","journal-title":"Annu Rev Biochem"},{"key":"key20180919081436_B22","doi-asserted-by":"publisher","first-page":"3861","DOI":"10.1128\/JB.00178-10","article-title":"Multiple signals direct the assembly and function of a type 1 secretion system","volume":"192","year":"2010","journal-title":"J Bacteriol"},{"key":"key20180919081436_B23","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1146\/annurev-micro-090110-102943","article-title":"Structure and function of MARTX toxins and other large repetitive RTX proteins","volume":"65","year":"2011","journal-title":"Annu Rev Microbiol"},{"key":"key20180919081436_B24","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.bbamcr.2004.05.001","article-title":"Type I secretion in Gram-negative bacteria","volume":"1694","year":"2004","journal-title":"Biochim Biophys Acta"},{"key":"key20180919081436_B25","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1101\/gr.7229808","article-title":"Multigenome analysis identifies a worldwide distributed epidemic Legionella pneumophila clone that emerged within a highly diverse species","volume":"18","year":"2008","journal-title":"Genome Res"},{"key":"key20180919081436_B26","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1128\/IAI.69.1.508-517.2001","article-title":"Legionella pneumophila entry gene rtxA is involved in virulence","volume":"69","year":"2001","journal-title":"Infect Immun"},{"issue":"Pt 6","key":"key20180919081436_B27","first-page":"1667","article-title":"Role of the Legionella pneumophila rtxA gene in amoebae","volume":"148","year":"2002","journal-title":"Microbiology"},{"key":"key20180919081436_B28","doi-asserted-by":"publisher","first-page":"1936","DOI":"10.1128\/IAI.00805-10","article-title":"Protein kinase LegK2 is a type IV secretion system effector involved in endoplasmic reticulum recruitment and intracellular replication of Legionella pneumophila","volume":"79","year":"2011","journal-title":"Infect Immun"},{"issue":"8","key":"key20180919081436_B29","doi-asserted-by":"publisher","first-page":"e1000117","DOI":"10.1371\/journal.ppat.1000117","article-title":"Legionella eukaryotic-like type IV substrates interfere with organelle trafficking","volume":"4","year":"2008","journal-title":"PLoS Pathog"},{"key":"key20180919081436_B30","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1111\/j.1365-2958.1994.tb00343.x","article-title":"Mutagenesis of Legionella pneumophila using Tn903 dIIlacz: identification of a growth-phase-regulated pigmentation gene","volume":"11","year":"1994","journal-title":"Mol Microbiol"},{"key":"key20180919081436_B31","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1046\/j.1365-2958.1998.00680.x","article-title":"Evidence for pore-forming ability by Legionella pneumophila","volume":"27","year":"1998","journal-title":"Mol Microbiol"},{"issue":"11","key":"key20180919081436_B32","doi-asserted-by":"publisher","first-page":"e7732","DOI":"10.1371\/journal.pone.0007732","article-title":"The TolC protein of Legionella pneumophila plays a major role in multi-drug resistance and the early steps of host invasion","volume":"4","year":"2009","journal-title":"PLoS One"},{"key":"key20180919081436_B33","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1016\/j.resmic.2013.03.011","article-title":"Type I secretion systems\u2014a story of appendices","volume":"164","year":"2013","journal-title":"Res Microbiol"},{"key":"key20180919081436_B34","doi-asserted-by":"publisher","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","year":"1998","journal-title":"Mol Microbiol"},{"key":"key20180919081436_B35","doi-asserted-by":"publisher","first-page":"2568","DOI":"10.1074\/jbc.M111.318766","article-title":"Kinetic analysis of ribosome-bound fluorescent proteins reveals an early, stable, cotranslational folding intermediate","volume":"287","year":"2012","journal-title":"J Biol Chem"},{"key":"key20180919081436_B36","doi-asserted-by":"publisher","first-page":"4657","DOI":"10.1093\/emboj\/20.17.4657","article-title":"Folded HasA inhibits its own secretion through its ABC exporter","volume":"20","year":"2001","journal-title":"EMBO J"},{"key":"key20180919081436_B37","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1128\/IAI.00956-06","article-title":"Environmental mimics and the Lvh type IVA secretion system contribute to virulence-related phenotypes of Legionella pneumophila","volume":"75","year":"2007","journal-title":"Infect Immun"},{"key":"key20180919081436_B38","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1038\/ng1447","article-title":"Evidence in the Legionella pneumophila genome for exploitation of host cell functions and high genome plasticity","volume":"36","year":"2004","journal-title":"Nat Genet"},{"key":"key20180919081436_B39","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1126\/science.1099776","article-title":"The genomic sequence of the accidental pathogen Legionella pneumophila","volume":"305","year":"2004","journal-title":"Science"},{"key":"key20180919081436_B40","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1186\/1471-2164-12-536","article-title":"Extensive recombination events and horizontal gene transfer shaped the Legionella pneumophila genomes","volume":"12","year":"2011","journal-title":"BMC Genomics"},{"key":"key20180919081436_B41","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/j.ijmm.2007.03.009","article-title":"Legionella pathogenicity: genome structure, regulatory networks and the host cell response","volume":"297","year":"2007","journal-title":"Int J Med Microbiol"},{"key":"key20180919081436_B42","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1186\/1471-2164-11-181","article-title":"Legionella pneumophila pangenome reveals strain-specific virulence factors","volume":"11","year":"2010","journal-title":"BMC Genomics"},{"issue":"2","key":"key20180919081436_B43","doi-asserted-by":"publisher","first-page":"e1000587","DOI":"10.1371\/journal.pbio.1000587","article-title":"A c-di-GMP effector system controls cell adhesion by inside-out signaling and surface protein cleavage","volume":"9","year":"2011","journal-title":"PLoS Biol"},{"key":"key20180919081436_B44","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.resmic.2012.10.001","article-title":"Atomic force and super-resolution microscopy support a role for LapA as a cell-surface biofilm adhesin of Pseudomonas fluorescens","volume":"163","year":"2012","journal-title":"Res Microbiol"}],"container-title":["Journal of Bacteriology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1128\/JB.02164-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T17:39:46Z","timestamp":1627580386000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JB.02164-14"}},"subtitle":[],"editor":[{"given":"J. S.","family":"Parkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,11,24]]},"references-count":44,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,1,7]]},"published-print":{"date-parts":[[2015,2,1]]}},"alternative-id":["10.1128\/JB.02164-14"],"URL":"https:\/\/doi.org\/10.1128\/jb.02164-14","relation":{},"ISSN":["0021-9193","1098-5530"],"issn-type":[{"value":"0021-9193","type":"print"},{"value":"1098-5530","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,24]]}}}