{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T07:50:12Z","timestamp":1776325812256,"version":"3.50.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T00:00:00Z","timestamp":1557187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001736","name":"German-Israeli Foundation for Scientific Research and Development","doi-asserted-by":"publisher","award":["1096-39.11\/2010"],"award-info":[{"award-number":["1096-39.11\/2010"]}],"id":[{"id":"10.13039\/501100001736","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001736","name":"German-Israeli Foundation for Scientific Research and Development","doi-asserted-by":"publisher","award":["I-41-416.6-2017"],"award-info":[{"award-number":["I-41-416.6-2017"]}],"id":[{"id":"10.13039\/501100001736","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001736","name":"German-Israeli Foundation for Scientific Research and Development","doi-asserted-by":"publisher","award":["1096-39.11\/2010"],"award-info":[{"award-number":["1096-39.11\/2010"]}],"id":[{"id":"10.13039\/501100001736","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Infect-Era \/Chief Scientist Ministry of Health","award":["3-12435"],"award-info":[{"award-number":["3-12435"]}]},{"name":"Infect-Era \/Chief Scientist Ministry of Health","award":["2616\/18"],"award-info":[{"award-number":["2616\/18"]}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"crossref","award":["031L0093B"],"award-info":[{"award-number":["031L0093B"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["SFB 900 TP8"],"award-info":[{"award-number":["SFB 900 TP8"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["SPP1656\/2"],"award-info":[{"award-number":["SPP1656\/2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Salmonella enterica serovar Infantis (S. Infantis) is one of the ubiquitous serovars of the bacterial pathogen S. enterica and recently has been emerging in many countries worldwide. Nonetheless, not much is known about its epidemiology, host adaptation, and virulence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Epidemiological and molecular approaches were used together with tissue-culture and mouse models to conduct phenotypic comparison with the model S. enterica serovar Typhimurium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We show that S. Infantis is more frequently associated with infections in infants &lt;2 years old and prone to cause significantly less invasive infections than serovar Typhimurium. Moreover, although S. Infantis adheres better to host cells and highly colonizes mouse intestines soon after infection, it is significantly less invasive and induces much lower inflammation and disease in vivo than S. Typhimurium. These differences were associated with lower expression of Salmonella pathogenicity island (SPI) 1 genes in S. Infantis than in S. Typhimurium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results demonstrate previously unknown differences in the epidemiology, virulence pathway expression, and pathogenicity between two highly abundant Salmonella serovars and suggest that native variation in the expression of the SPI-1 regulon is likely to contribute to epidemiological and virulence variation between genetically similar nontyphoidal Salmonella serovars.<\/jats:p><\/jats:sec>","DOI":"10.1093\/infdis\/jiz235","type":"journal-article","created":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T17:03:48Z","timestamp":1557248628000},"page":"1071-1081","source":"Crossref","is-referenced-by-count":24,"title":["Differences in the expression of SPI-1 genes pathogenicity and epidemiology between the emerging Salmonella enterica serovar Infantis and the model Salmonella enterica serovar Typhimurium"],"prefix":"10.1093","volume":"220","author":[{"given":"Gili","family":"Aviv","sequence":"first","affiliation":[{"name":"The Infectious Diseases Research Laboratory, Sheba Medical Center, Tel-Hashomer"},{"name":"Department of Clinical Microbiology and Immunology, Jerusalem, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antje","family":"Cornelius","sequence":"additional","affiliation":[{"name":"Research Center Borstel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maya","family":"Davidovich","sequence":"additional","affiliation":[{"name":"Central Laboratories, Ministry of Health, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helit","family":"Cohen","sequence":"additional","affiliation":[{"name":"The Infectious Diseases Research Laboratory, Sheba Medical Center, Tel-Hashomer"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdulhadi","family":"Suwandi","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School and German Center for Infection Research, Partner Site Hannover-Braunschweig"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alibek","family":"Galeev","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School and German Center for Infection Research, Partner Site Hannover-Braunschweig"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Steck","sequence":"additional","affiliation":[{"name":"Research Center Borstel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shalhevet","family":"Azriel","sequence":"additional","affiliation":[{"name":"The Infectious Diseases Research Laboratory, Sheba Medical Center, Tel-Hashomer"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Assaf","family":"Rokney","sequence":"additional","affiliation":[{"name":"Central Laboratories, Ministry of Health, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lea","family":"Valinsky","sequence":"additional","affiliation":[{"name":"Central Laboratories, Ministry of Health, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galia","family":"Rahav","sequence":"additional","affiliation":[{"name":"The Infectious Diseases Research Laboratory, Sheba Medical Center, Tel-Hashomer"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3718-2090","authenticated-orcid":false,"given":"Guntram A","family":"Grassl","sequence":"additional","affiliation":[{"name":"Research Center Borstel, Germany"},{"name":"Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School and German Center for Infection Research, Partner Site Hannover-Braunschweig"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ohad","family":"Gal-Mor","sequence":"additional","affiliation":[{"name":"The Infectious Diseases Research Laboratory, Sheba Medical Center, Tel-Hashomer"},{"name":"Department of Clinical Microbiology and Immunology, Jerusalem, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,5,7]]},"reference":[{"key":"2019080903145588400_CIT0001","article-title":"Persistent infection and long-term carriage of typhoidal and nontyphoidal salmonellae","volume":"32:e00088\u201318","author":"Gal-Mor","year":"2019","journal-title":"Clin Microbiol Rev"},{"key":"2019080903145588400_CIT0002","doi-asserted-by":"crossref","first-page":"e1001923","DOI":"10.1371\/journal.pmed.1001923","article-title":"World Health Organization global estimates and regional comparisons of the burden of foodborne disease in 2010","volume":"12","author":"Havelaar","year":"2015","journal-title":"PLoS Med"},{"key":"2019080903145588400_CIT0003","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1086\/318457","article-title":"Nontyphoidal salmonellosis","volume":"32","author":"Hohmann","year":"2001","journal-title":"Clin Infect Dis"},{"key":"2019080903145588400_CIT0004","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1111\/j.1462-5822.2011.01701.x","article-title":"Salmonella effectors: important players modulating host cell function during infection","volume":"13","author":"Agbor","year":"2011","journal-title":"Cell Microbiol"},{"key":"2019080903145588400_CIT0005","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.coi.2011.06.004","article-title":"Salmonella Typhimurium diarrhea: switching the mucosal epithelium from homeostasis to defense","volume":"23","author":"Kaiser","year":"2011","journal-title":"Curr Opin Immunol"},{"key":"2019080903145588400_CIT0006","volume-title":"Annual epidemiological report on communicable diseases in Europe 2009","author":"European Centre for Disease Prevention and Control","year":"2009"},{"key":"2019080903145588400_CIT0007","volume-title":"National enteric disease surveillance: Salmonella annual report, 2016","author":"Centers for Disease Control and Prevention","year":"2018"},{"key":"2019080903145588400_CIT0008","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1111\/1462-2920.12351","article-title":"A unique megaplasmid contributes to stress tolerance and pathogenicity of an emergent Salmonella enterica serovar Infantis strain","volume":"16","author":"Aviv","year":"2014","journal-title":"Environ Microbiol"},{"key":"2019080903145588400_CIT0009","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.3201\/eid1611.100100","article-title":"Multidrug-resistant Salmonella enterica serovar Infantis, Israel","volume":"16","author":"Gal-Mor","year":"2010","journal-title":"Emerg Infect Dis"},{"key":"2019080903145588400_CIT0010","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1128\/AAC.01514-06","article-title":"Dissemination of an extended-spectrum-beta-lactamase blaTEM-52 gene-carrying IncI1 plasmid in various Salmonella enterica serovars isolated from poultry and humans in Belgium and France between 2001 and 2005","volume":"51","author":"Cloeckaert","year":"2007","journal-title":"Antimicrob Agents Chemother"},{"key":"2019080903145588400_CIT0011","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1089\/fpd.2011.1038","article-title":"Clonal dissemination of Salmonella enterica serovar Infantis in Germany","volume":"9","author":"Hauser","year":"2012","journal-title":"Foodborne Pathog Dis"},{"key":"2019080903145588400_CIT0012","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ijfoodmicro.2008.07.005","article-title":"Prevalence and characterization of Salmonella infantis isolates originating from different points of the broiler chicken-human food chain in Hungary","volume":"127","author":"N\u00f3gr\u00e1dy","year":"2008","journal-title":"Int J Food Microbiol"},{"key":"2019080903145588400_CIT0013","doi-asserted-by":"crossref","first-page":"4885","DOI":"10.1128\/JCM.42.10.4885-4888.2004","article-title":"Pediatric infection due to multiresistant Salmonella enterica serotype Infantis in Honduras","volume":"42","author":"Liebana","year":"2004","journal-title":"J Clin Microbiol"},{"key":"2019080903145588400_CIT0014","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.vetmic.2009.07.007","article-title":"Genetic analysis of multi-drug resistance and the clonal dissemination of beta-lactam resistance in Salmonella Infantis isolated from broilers","volume":"140","author":"Shahada","year":"2010","journal-title":"Vet Microbiol"},{"key":"2019080903145588400_CIT0015","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/j.1574-695X.2008.00435.x","article-title":"A comparison of three molecular typing methods for the discrimination of Salmonella enterica serovar Infantis","volume":"53","author":"Ross","year":"2008","journal-title":"FEMS Immunol Med Microbiol"},{"key":"2019080903145588400_CIT0016","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.resmic.2009.10.002","article-title":"Supplement 2003-2007 (No. 47) to the White-Kauffmann-Le Minor scheme","volume":"161","author":"Guibourdenche","year":"2010","journal-title":"Res Microbiol"},{"key":"2019080903145588400_CIT0017","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1128\/IAI.01135-15","article-title":"The stringent response regulator DksA is required for Salmonella enterica serovar Typhimurium growth in minimal medium, motility, biofilm formation, and intestinal colonization","volume":"84","author":"Azriel","year":"2016","journal-title":"Infect Immun"},{"key":"2019080903145588400_CIT0018","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1016\/j.micinf.2006.04.015","article-title":"The temperature-sensing protein TlpA is repressed by PhoP and dispensable for virulence of Salmonella enterica serovar Typhimurium in mice","volume":"8","author":"Gal-Mor","year":"2006","journal-title":"Microbes Infect"},{"key":"2019080903145588400_CIT0019","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.3389\/fmicb.2016.01468","article-title":"Genetic and phenotypic characterization of a Salmonella enterica serovar enteritidis emerging strain with superior intra-macrophage replication phenotype","volume":"7","author":"Shomer","year":"2016","journal-title":"Front Microbiol"},{"key":"2019080903145588400_CIT0020","article-title":"Differences in host cell invasion and SPI-1 expression between Salmonella enterica serovar Paratyphi A and the non-typhoidal serovar Typhimurium. Infection and immunity","author":"Elhadad","year":"2016; 84:1150\u20131165"},{"key":"2019080903145588400_CIT0021","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1053\/j.gastro.2007.12.043","article-title":"Chronic enteric salmonella infection in mice leads to severe and persistent intestinal fibrosis","volume":"134","author":"Grassl","year":"2008","journal-title":"Gastroenterology"},{"key":"2019080903145588400_CIT0022","doi-asserted-by":"crossref","first-page":"E1277","DOI":"10.1073\/pnas.1201061109","article-title":"The transcriptional landscape and small RNAs of Salmonella enterica serovar Typhimurium","volume":"109","author":"Kroger","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2019080903145588400_CIT0023","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01395-16","article-title":"Horizontal transfer of the Salmonella enterica serovar infantis resistance and virulence plasmid pESI to the gut microbiota of warm-blooded hosts","volume":"7","author":"Aviv","year":"2016","journal-title":"mBio"},{"key":"2019080903145588400_CIT0024","doi-asserted-by":"crossref","first-page":"2901","DOI":"10.1128\/IAI.59.9.2901-2908.1991","article-title":"Distribution of the invA, -B, -C, and -D genes of Salmonella Typhimurium among other Salmonella serovars: invA mutants of Salmonella Typhi are deficient for entry into mammalian cells","volume":"59","author":"Gal\u00e1n","year":"1991","journal-title":"Infect Immun"},{"key":"2019080903145588400_CIT0025","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/j.1574-695X.2006.00051.x","article-title":"Neutrophil influx during non-typhoidal salmonellosis: who is in the driver\u2019s seat?","volume":"46","author":"T\u00fckel","year":"2006","journal-title":"FEMS Immunol Med Microbiol"},{"key":"2019080903145588400_CIT0026","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1007\/s00284-013-0307-8","article-title":"Salmonella pathogenicity island 1(SPI-1) at work","volume":"66","author":"Que","year":"2013","journal-title":"Curr Microbiol"},{"key":"2019080903145588400_CIT0027","doi-asserted-by":"crossref","first-page":"4099","DOI":"10.1128\/IAI.67.8.4099-4105.1999","article-title":"Differential regulation of Salmonella Typhimurium type III secreted proteins by pathogenicity island 1 (SPI-1)-encoded transcriptional activators InvF and hilA","volume":"67","author":"Eichelberg","year":"1999","journal-title":"Infect Immun"},{"key":"2019080903145588400_CIT0028","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1128\/JCM.00399-14","article-title":"Integrative analysis of salmonellosis in Israel reveals association of Salmonella enterica serovar 9,12:l,v:- with extraintestinal infections, dissemination of endemic S. enterica serovar Typhimurium DT104 biotypes, and severe underreporting of outbreaks","volume":"52","author":"Marzel","year":"2014","journal-title":"J Clin Microbiol"},{"key":"2019080903145588400_CIT0029","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1017\/S095026880006711X","article-title":"Extraintestinal salmonellosis","volume":"100","author":"Wilkins","year":"1988","journal-title":"Epidemiol Infect"},{"key":"2019080903145588400_CIT0030","doi-asserted-by":"crossref","first-page":"S149","DOI":"10.1086\/381581","article-title":"Invasive Salmonella infections in the United States, FoodNet, 1996\u20131999: incidence, serotype distribution, and outcome","volume":"38","author":"Vugia","year":"2004","journal-title":"Clin Infect Dis"},{"key":"2019080903145588400_CIT0031","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/nrmicro3428","article-title":"Now you see me, now you don\u2019t: the interaction of Salmonella with innate immune receptors","volume":"13","author":"Keestra-Gounder","year":"2015","journal-title":"Nat Rev Microbiol"},{"key":"2019080903145588400_CIT0032","doi-asserted-by":"crossref","first-page":"88","DOI":"10.4161\/gmic.18602","article-title":"Typhoid fever: \u201cyou can\u2019t hit what you can\u2019t see\u201d","volume":"3","author":"Wangdi","year":"2012","journal-title":"Gut Microbes"},{"key":"2019080903145588400_CIT0033","doi-asserted-by":"crossref","first-page":"e1004207","DOI":"10.1371\/journal.ppat.1004207","article-title":"Salmonella enterica serovar Typhi conceals the invasion-associated type three secretion system from the innate immune system by gene regulation","volume":"10","author":"Winter","year":"2014","journal-title":"PLoS Pathog"},{"key":"2019080903145588400_CIT0034","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1093\/infdis\/jiu663","article-title":"Feverlike temperature is a virulence regulatory cue controlling the motility and host cell entry of typhoidal Salmonella","volume":"212","author":"Elhadad","year":"2015","journal-title":"J Infect Dis"},{"key":"2019080903145588400_CIT0035","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1099\/mic.0.048496-0","article-title":"Differences in Salmonella enterica serovar Typhimurium strain invasiveness are associated with heterogeneity in SPI-1 gene expression","volume":"157","author":"Clark","year":"2011","journal-title":"Microbiology"},{"key":"2019080903145588400_CIT0036","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1146\/annurev.cellbio.17.1.53","article-title":"Salmonella interactions with host cells: type III secretion at work","volume":"17","author":"Gal\u00e1n","year":"2001","journal-title":"Annu Rev Cell Dev Biol"},{"key":"2019080903145588400_CIT0037","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.tim.2005.08.008","article-title":"A mouse model for S. Typhimurium-induced enterocolitis","volume":"13","author":"Hapfelmeier","year":"2005","journal-title":"Trends Microbiol"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiz235\/29025294\/jiz235.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jid\/article-pdf\/220\/6\/1071\/29113172\/jiz235.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T00:19:36Z","timestamp":1607645976000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/220\/6\/1071\/5486384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,7]]},"references-count":37,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,5,7]]},"published-print":{"date-parts":[[2019,8,9]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiz235","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,9,15]]},"published":{"date-parts":[[2019,5,7]]}}}