{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T18:38:18Z","timestamp":1792694298741,"version":"4.5.0"},"reference-count":98,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1186371"],"award-info":[{"award-number":["APP1186371"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1175976"],"award-info":[{"award-number":["APP1175976"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP2037421"],"award-info":[{"award-number":["APP2037421"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1196945"],"award-info":[{"award-number":["APP1196945"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP2021638"],"award-info":[{"award-number":["APP2021638"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004412","name":"Human Frontier Science Program","doi-asserted-by":"publisher","award":["RGP013\/2023-S4S"],"award-info":[{"award-number":["RGP013\/2023-S4S"]}],"id":[{"id":"10.13039\/100004412","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Legionella pneumophila is the causative agent of Legionnaires\u2019 disease, an accidental and severe form of pneumonia. The replication of\n                    <jats:italic>L. pneumophila<\/jats:italic>\n                    within alveolar macrophages requires the Dot\/Icm type IV secretion system that translocates more than 330 bacterial effector proteins into the infected host cell. Many Dot\/Icm effectors possess eukaryotic-like domains and manipulate host processes by functional mimicry. However, only a minority of effectors have been fully characterized. Redundancy among effector protein activities and host targets has complicated functional characterization of individual effector proteins. To explore the collective impact of Dot\/Icm effectors on host cell processes, we created a library of 14\n                    <jats:italic>L. pneumophila<\/jats:italic>\n                    genomic mutant strains lacking effector-rich regions (a total of 85 effector genes deleted) and used the multi-deletion mutants to interrogate host-pathogen interactions. While none of the mutants exhibited a defect in intracellular replication in THP-1 macrophages, several were attenuated in amoebae, including a mutant lacking a predicted amino acid transporter. In THP-1 cells, we observed that wild-type\n                    <jats:italic>L. pneumophila<\/jats:italic>\n                    130b triggered a strong inflammatory and cellular stress transcriptional response in macrophages, whereas six mutants displayed reduced interferon signalling and one mutant displayed a marked decrease in the global expression of host heat shock response (HSR) genes. Through the creation of further sub-deletions, we found that the Dot\/Icm effector kinase LegK4 was responsible for induction of the host HSR via the canonical transcription factor heat shock factor 1 (HSF1). Infection of THP-1 macrophages deficient in\n                    <jats:italic>HSF1<\/jats:italic>\n                    revealed a potential role for the host HSR in the early stages of\n                    <jats:italic>L. pneumophila<\/jats:italic>\n                    infection. Together, these results reinforce the utility of multi-gene deletions to identify Dot\/Icm effector phenotypes and the importance of the host HSR to\n                    <jats:italic>L. pneumophila<\/jats:italic>\n                    infection.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014083","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:41:51Z","timestamp":1792690911000},"page":"e1014083","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-Dot\/Icm effector mutants reveal distinct host responses in Legionella infected macrophages"],"prefix":"10.1371","volume":"22","author":[{"given":"Raissa","family":"Wibawa","sequence":"first","affiliation":[{"name":"Hudson Institute of Medical Research","place":["Clayton, Australia"],"department":["Centre for Innate Immunity and Infectious Diseases"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Li","sequence":"additional","affiliation":[{"name":"Hudson Institute of Medical Research","place":["Clayton, Australia"],"department":["Centre for Innate Immunity and Infectious Diseases"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linden J.","family":"Gearing","sequence":"additional","affiliation":[{"name":"Hudson Institute of Medical Research","place":["Clayton, Australia"],"department":["Centre for Innate Immunity and Infectious Diseases"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sacha","family":"Pidot","sequence":"additional","affiliation":[{"name":"University of Melbourne at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"],"department":["Department of Microbiology and Immunology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2982-3919","authenticated-orcid":true,"given":"Yuliia","family":"Faidiuk","sequence":"additional","affiliation":[{"name":"Hudson Institute of Medical Research","place":["Clayton, Australia"],"department":["Centre for Innate Immunity and Infectious Diseases"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson","family":"Wong","sequence":"additional","affiliation":[{"name":"Hudson Institute of Medical Research","place":["Clayton, Australia"],"department":["Centre for Innate Immunity and Infectious Diseases"]},{"name":"Monash University","place":["Clayton, Australia"],"department":["Department of Molecular and Translational Science"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garrett Z.","family":"Ng","sequence":"additional","affiliation":[{"name":"Hudson Institute of Medical Research","place":["Clayton, Australia"],"department":["Centre for Innate Immunity and Infectious Diseases"]},{"name":"Monash University","place":["Clayton, Australia"],"department":["Department of Molecular and Translational Science"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"McCaffrey","sequence":"additional","affiliation":[{"name":"Hudson Institute of Medical Research","place":["Clayton, Australia"],"department":["Centre for Innate Immunity and Infectious Diseases"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Hertzog","sequence":"additional","affiliation":[{"name":"Hudson Institute of Medical Research","place":["Clayton, Australia"],"department":["Centre for Innate Immunity and Infectious Diseases"]},{"name":"Monash University","place":["Clayton, Australia"],"department":["Department of Molecular and Translational Science"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivani","family":"Pasricha","sequence":"additional","affiliation":[{"name":"University of Melbourne at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"],"department":["Department of Infectious Diseases"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4254-2863","authenticated-orcid":true,"given":"Elizabeth L.","family":"Hartland","sequence":"additional","affiliation":[{"name":"Hudson Institute of Medical Research","place":["Clayton, Australia"],"department":["Centre for Innate Immunity and Infectious Diseases"]},{"name":"Monash University","place":["Clayton, Australia"],"department":["Department of Molecular and Translational Science"]},{"name":"University of Melbourne at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"],"department":["Department of Infectious Diseases"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"ppat.1014083.ref001","doi-asserted-by":"crossref","DOI":"10.1017\/S0950268823001206","article-title":"Legionellosis on the rise: A scoping review of sporadic, community-acquired incidence in the United States","volume":"151","author":"MA Moffa","year":"2023","journal-title":"Epidemiol Infect"},{"issue":"3","key":"ppat.1014083.ref002","article-title":"Mysteriously rapid rise in Legionnaires\u2019 disease incidence correlates with declining atmospheric sulfur dioxide","volume":"3","author":"F Yu","year":"2024","journal-title":"PNAS Nexus"},{"key":"ppat.1014083.ref003","volume-title":"CDC yellow book 2020: health information for international travel","year":"2019"},{"issue":"6","key":"ppat.1014083.ref004","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1073\/pnas.1808016116","article-title":"More than 18,000 effectors in the Legionella genus genome provide multiple, independent combinations for replication in human cells","volume":"116","author":"L Gomez-Valero","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"issue":"20","key":"ppat.1014083.ref005","doi-asserted-by":"crossref","first-page":"9607","DOI":"10.1073\/pnas.89.20.9607","article-title":"Identification of a Legionella pneumophila locus required for intracellular multiplication in human macrophages","volume":"89","author":"A Marra","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"ppat.1014083.ref006","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1365-2958.1993.tb01092.x","article-title":"Two distinct defects in intracellular growth complemented by a single genetic locus in Legionella pneumophila","volume":"7","author":"KH Berger","year":"1993","journal-title":"Mol 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Tan","year":"2011","journal-title":"Nature"},{"issue":"10","key":"ppat.1014083.ref013","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.15252\/embr.201743903","article-title":"ER remodeling by the large GTPase atlastin promotes vacuolar growth of Legionella pneumophila","volume":"18","author":"B Steiner","year":"2017","journal-title":"EMBO Rep"},{"issue":"16","key":"ppat.1014083.ref014","doi-asserted-by":"crossref","first-page":"6405","DOI":"10.1074\/jbc.RA118.007086","article-title":"The Legionella effector RavD binds phosphatidylinositol-3-phosphate and helps suppress endolysosomal maturation of the Legionella-containing vacuole","volume":"294","author":"CM Pike","year":"2019","journal-title":"J Biol Chem"},{"issue":"6","key":"ppat.1014083.ref015","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.02420-18","article-title":"Legionella-containing vacuoles capture PtdIns(4)P-rich vesicles derived from the Golgi apparatus","volume":"9","author":"S 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binds to the bacterial effector LpnE","volume":"11","author":"SS Weber","year":"2009","journal-title":"Cell Microbiol"},{"issue":"2","key":"ppat.1014083.ref019","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.chom.2016.12.007","article-title":"A Single Legionella effector catalyzes a multistep ubiquitination pathway to rearrange tubular endoplasmic reticulum for replication","volume":"21","author":"KM Kotewicz","year":"2017","journal-title":"Cell Host Microbe"},{"issue":"7","key":"ppat.1014083.ref020","doi-asserted-by":"crossref","DOI":"10.1111\/cmi.12840","article-title":"LotA, a Legionella deubiquitinase, has dual catalytic activity and contributes to intracellular growth","volume":"20","author":"T Kubori","year":"2018","journal-title":"Cell Microbiol"},{"issue":"7601","key":"ppat.1014083.ref021","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/nature17657","article-title":"Ubiquitination independent of E1 and E2 enzymes by bacterial effectors","volume":"533","author":"J Qiu","year":"2016","journal-title":"Nature"},{"issue":"8020","key":"ppat.1014083.ref022","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/s41586-024-07573-z","article-title":"Legionella effector LnaB is a phosphoryl-AMPylase that impairs phosphosignalling","volume":"631","author":"T Wang","year":"2024","journal-title":"Nature"},{"issue":"8","key":"ppat.1014083.ref023","doi-asserted-by":"crossref","first-page":"3026","DOI":"10.1128\/JB.01798-07","article-title":"Lgt: a family of cytotoxic glucosyltransferases produced by Legionella pneumophila","volume":"190","author":"Y Belyi","year":"2008","journal-title":"J Bacteriol"},{"issue":"3","key":"ppat.1014083.ref024","article-title":"A Legionella pneumophila Kinase phosphorylates the Hsp70 chaperone family to inhibit eukaryotic protein synthesis","volume":"25","author":"SM Moss","year":"2019","journal-title":"Cell Host 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Ellis","year":"2023","journal-title":"Elife"},{"issue":"36","key":"ppat.1014083.ref043","doi-asserted-by":"crossref","first-page":"14733","DOI":"10.1073\/pnas.1111678108","article-title":"Minimization of the Legionella pneumophila genome reveals chromosomal regions involved in host range expansion","volume":"108","author":"TJ O\u2019Connor","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"issue":"5","key":"ppat.1014083.ref044","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1111\/j.1600-0854.2010.01050.x","article-title":"Legionella pneumophila promotes functional interactions between plasma membrane syntaxins and Sec22b","volume":"11","author":"K Arasaki","year":"2010","journal-title":"Traffic"},{"issue":"6110","key":"ppat.1014083.ref045","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1126\/science.1227026","article-title":"The Legionella effector RavZ inhibits host autophagy through irreversible Atg8 deconjugation","volume":"338","author":"A 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Ma","year":"2012","journal-title":"Nature"},{"issue":"12","key":"ppat.1014083.ref055","doi-asserted-by":"crossref","DOI":"10.1128\/jb.00324-24","article-title":"Legionella pneumophila, a Rosetta stone to understanding bacterial pathogenesis","volume":"206","author":"KA Romanov","year":"2024","journal-title":"J Bacteriol"},{"key":"ppat.1014083.ref056","doi-asserted-by":"crossref","first-page":"1787137","DOI":"10.3389\/fcimb.2026.1787137","article-title":"Molecular evolution and adaptations of Legionella pneumophila from amoebae hosts to macrophages","volume":"16","author":"CJ Shin","year":"2026","journal-title":"Front Cell Infect Microbiol"},{"issue":"1","key":"ppat.1014083.ref057","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology","volume":"25","author":"M Ashburner","year":"2000","journal-title":"Nat 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Ghosh","year":"2017","journal-title":"Front Cell Infect Microbiol"},{"issue":"12","key":"ppat.1014083.ref068","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1001216","article-title":"Legionella metaeffector exploits host proteasome to temporally regulate cognate effector","volume":"6","author":"T Kubori","year":"2010","journal-title":"PLoS Pathog"},{"issue":"1","key":"ppat.1014083.ref069","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.02182-16","article-title":"A Unique cis-encoded small noncoding RNA Is Regulating Legionella pneumophila Hfq expression in a life cycle-dependent manner","volume":"8","author":"G Oliva","year":"2017","journal-title":"mBio"},{"issue":"3","key":"ppat.1014083.ref070","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1128\/JB.06112-11","article-title":"Lag phase is a distinct growth phase that prepares bacteria for exponential growth and involves transient metal accumulation","volume":"194","author":"MD Rolfe","year":"2012","journal-title":"J Bacteriol"},{"issue":"21","key":"ppat.1014083.ref071","doi-asserted-by":"crossref","first-page":"3431","DOI":"10.1101\/gad.12.21.3431","article-title":"Bacterial senescence: stasis results in increased and differential oxidation of cytoplasmic proteins leading to developmental induction of the heat shock regulon","volume":"12","author":"S Dukan","year":"1998","journal-title":"Genes Dev"},{"issue":"5","key":"ppat.1014083.ref072","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1111\/j.1365-2958.2005.04490.x","article-title":"Intracellular multiplication of Legionella pneumophila depends on host cell amino acid transporter SLC1A5","volume":"55","author":"H Wieland","year":"2005","journal-title":"Mol Microbiol"},{"issue":"12","key":"ppat.1014083.ref073","article-title":"The transcriptome of Legionella pneumophila-infected human monocyte-derived macrophages","volume":"9","author":"CTD Price","year":"2014","journal-title":"PLoS One"},{"issue":"30","key":"ppat.1014083.ref074","doi-asserted-by":"crossref","first-page":"21040","DOI":"10.1074\/jbc.M114.570085","article-title":"Amino acid uptake and metabolism of Legionella pneumophila Hosted by Acanthamoeba castellanii","volume":"289","author":"E Schunder","year":"2014","journal-title":"J Biol Chem"},{"issue":"7","key":"ppat.1014083.ref075","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1128\/IAI.66.7.3029-3034.1998","article-title":"Expression of Legionella pneumophila virulence traits in response to growth conditions","volume":"66","author":"B Byrne","year":"1998","journal-title":"Infect Immun"},{"issue":"2","key":"ppat.1014083.ref076","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/BF01567708","article-title":"Metabolic pathways and nitrogen metabolism in Legionella pneumophila","volume":"11","author":"MG Keen","year":"1984","journal-title":"Current Microbiology"},{"issue":"1","key":"ppat.1014083.ref077","article-title":"A Legionella 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Bar-Lavan","year":"2016","journal-title":"Essays Biochem"},{"key":"ppat.1014083.ref084","author":"T Seemann","year":"2015"},{"issue":"5","key":"ppat.1014083.ref085","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1089\/cmb.2012.0021","article-title":"SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing","volume":"19","author":"A Bankevich","year":"2012","journal-title":"J Comput Biol"},{"key":"ppat.1014083.ref086","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkae410","article-title":"The Galaxy platform for accessible, reproducible, and collaborative data analyses: 2024 update","volume":"52","author":"Galaxy Community","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"ppat.1014083.ref087","author":"S Andrews"},{"issue":"1","key":"ppat.1014083.ref088","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"A 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