{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T20:39:12Z","timestamp":1765485552740},"reference-count":64,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2011,4,11]],"date-time":"2011-04-11T00:00:00Z","timestamp":1302480000000},"content-version":"unspecified","delay-in-days":10,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Expert Rev. Mol. Med."],"published-print":{"date-parts":[[2011,4]]},"abstract":"<jats:p><jats:italic>Salmonella enterica<\/jats:italic>causes a range of life-threatening diseases in humans and animals worldwide. Current treatments for<jats:italic>S. enterica<\/jats:italic>infections are not sufficiently effective, and there is a need to develop new vaccines and therapeutics. An understanding of how<jats:italic>S. enterica<\/jats:italic>spreads in tissues has very important implications for targeting bacteria with vaccine-induced immune responses and antimicrobial drugs. Development of new control strategies would benefit from a more sophisticated evaluation of bacterial location, spatiotemporal patterns of spread and distribution in the tissues, and sites of microbial persistence. We review here recent studies of<jats:italic>S. enterica<\/jats:italic>serovar Typhimurium (<jats:italic>S<\/jats:italic>. Typhimurium) infections in mice, an established model of systemic typhoid fever in humans, which suggest that continuous bacterial spread to new infection foci and host phagocytes is an essential trait in the virulence of<jats:italic>S. enterica<\/jats:italic>during systemic infections. We further highlight how infections within host tissues are truly heterogeneous processes despite the fact that they are caused by the expansion of a genetically homogeneous microbial population. We conclude by discussing how understanding the within-host quantitative, spatial and temporal dynamics of<jats:italic>S. enterica<\/jats:italic>infections might aid the development of novel targeted preventative measures and drug regimens.<\/jats:p>","DOI":"10.1017\/s1462399411001840","type":"journal-article","created":{"date-parts":[[2011,10,18]],"date-time":"2011-10-18T11:34:19Z","timestamp":1318937659000},"source":"Crossref","is-referenced-by-count":51,"title":["Spread of<i>Salmonella enterica<\/i>in the body during systemic infection: unravelling host and pathogen determinants"],"prefix":"10.1017","volume":"13","author":[{"given":"Pietro","family":"Mastroeni","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Grant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2011,4,11]]},"reference":[{"key":"S1462399411001840_ref34","first-page":"973","article-title":"The in vivo division and death rates of Salmonella Typhimurium in the spleens of naturally resistant and susceptible mice measured by the superinfecting phage technique of Meynell","volume":"41","author":"Hormaeche","year":"1980","journal-title":"Immunology"},{"key":"S1462399411001840_ref43","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.10.5881-5891.2003"},{"key":"S1462399411001840_ref57","doi-asserted-by":"publisher","DOI":"10.1126\/science.1114383"},{"key":"S1462399411001840_ref11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.5.2396"},{"key":"S1462399411001840_ref26","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.4.569"},{"key":"S1462399411001840_ref42","first-page":"247","article-title":"T cells do not mediate the initial suppression of a Salmonella infection in the RES","volume":"70","author":"Hormaeche","year":"1990","journal-title":"Immunology"},{"key":"S1462399411001840_ref56","doi-asserted-by":"publisher","DOI":"10.1126\/science.1118711"},{"key":"S1462399411001840_ref23","first-page":"74","article-title":"The kinetics of blood clearance of isotopically labeled Salmonella Enteritidis by the reticuloendothelial system in mice","volume":"3","author":"Biozzi","year":"1960","journal-title":"Immunology"},{"key":"S1462399411001840_ref2","doi-asserted-by":"publisher","DOI":"10.1086\/649541"},{"key":"S1462399411001840_ref1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399407000373"},{"key":"S1462399411001840_ref48","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00827-09"},{"key":"S1462399411001840_ref12","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01341-08"},{"key":"S1462399411001840_ref24","doi-asserted-by":"publisher","DOI":"10.1016\/0882-4010(91)90013-Z"},{"key":"S1462399411001840_ref30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0060074"},{"key":"S1462399411001840_ref65","unstructured":"http:\/\/www.hhmi.org\/biointeractive\/disease\/animations.html. The web page from the World Health Organization has information about Salmonella:"},{"key":"S1462399411001840_ref33","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5458.1655"},{"key":"S1462399411001840_ref15","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.8.4795-4803.2003"},{"key":"S1462399411001840_ref38","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2001.00150.x"},{"key":"S1462399411001840_ref64","unstructured":"http:\/\/www.ecosal.org. The web page from the Howard Hughes Medical Institute has an animated movie of S. Typhimurium invading an epithelial cell of the intestinal tract, surviving the intracellular defense mechanisms of the host cell, and multiplying:"},{"key":"S1462399411001840_ref50","doi-asserted-by":"publisher","DOI":"10.1038\/nri1733"},{"key":"S1462399411001840_ref49","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1128\/MMBR.53.4.390-409.1989","article-title":"Pathogenesis and immunity in murine salmonellosis","volume":"53","author":"Hsu","year":"1989","journal-title":"Microbiology Reviews"},{"key":"S1462399411001840_ref40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0040349"},{"key":"S1462399411001840_ref45","doi-asserted-by":"crossref","first-page":"3355","DOI":"10.1128\/IAI.66.7.3355-3364.1998","article-title":"Susceptibility to Salmonella Typhimurium infection and effectiveness of vaccination in mice deficient in the tumor necrosis factor alpha p55 receptor","volume":"66","author":"Everest","year":"1998","journal-title":"Infection and Immunity"},{"key":"S1462399411001840_ref66","unstructured":"http:\/\/www.who.int\/topics\/salmonella\/en\/. The emergence, epidemiology and transmission of drug-resistant Salmonella:"},{"key":"S1462399411001840_ref29","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2003.00296.x"},{"key":"S1462399411001840_ref39","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(01)02098-4"},{"key":"S1462399411001840_ref47","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.02814.x"},{"key":"S1462399411001840_ref28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00679.x"},{"key":"S1462399411001840_ref22","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.2.551-557.2002"},{"key":"S1462399411001840_ref53","doi-asserted-by":"publisher","DOI":"10.1016\/0882-4010(86)90051-3"},{"key":"S1462399411001840_ref25","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2001.00137.x"},{"key":"S1462399411001840_ref14","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00417-06"},{"key":"S1462399411001840_ref19","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.4.1648"},{"key":"S1462399411001840_ref51","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000041107"},{"key":"S1462399411001840_ref55","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2034"},{"key":"S1462399411001840_ref3","first-page":"346","article-title":"The global burden of typhoid fever","volume":"82","author":"Crump","year":"2004","journal-title":"Bulletin of World Health Organization"},{"key":"S1462399411001840_ref46","doi-asserted-by":"crossref","first-page":"4767","DOI":"10.1128\/IAI.66.10.4767-4776.1998","article-title":"Interleukin-12 is required for control of the growth of attenuated aromatic-compound-dependent salmonellae in BALB\/c mice: role of gamma interferon and macrophage activation","volume":"66","author":"Mastroeni","year":"1998","journal-title":"Infection and Immunity"},{"key":"S1462399411001840_ref59","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/152.5.1044"},{"key":"S1462399411001840_ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2010.05.010"},{"key":"S1462399411001840_ref21","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00272-09"},{"key":"S1462399411001840_ref31","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.2.237"},{"key":"S1462399411001840_ref32","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.2.227"},{"key":"S1462399411001840_ref27","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.9.5726-5735.2001"},{"key":"S1462399411001840_ref44","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1128\/IAI.63.9.3674-3682.1995","article-title":"Effect of anti-tumor necrosis factor alpha antibodies on histopathology of primary Salmonella infections","volume":"63","author":"Mastroeni","year":"1995","journal-title":"Infection and Immunity"},{"key":"S1462399411001840_ref52","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.14.5189"},{"key":"S1462399411001840_ref8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006098107"},{"key":"S1462399411001840_ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2009.08.008"},{"key":"S1462399411001840_ref9","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2000.00035.x"},{"key":"S1462399411001840_ref13","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1960"},{"key":"S1462399411001840_ref18","doi-asserted-by":"publisher","DOI":"10.1038\/86373"},{"key":"S1462399411001840_ref6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33998"},{"key":"S1462399411001840_ref10","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/44593","article-title":"Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes","volume":"401","author":"Vazquez-Torres","year":"1999","journal-title":"Nature"},{"key":"S1462399411001840_ref20","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20052093"},{"key":"S1462399411001840_ref58","first-page":"9","article-title":"Comparative effect of gentamicin and pefloxacin treatment on the late stages of mouse typhoid","volume":"21","author":"Bonina","year":"1998","journal-title":"Microbiologica"},{"key":"S1462399411001840_ref7","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1788"},{"key":"S1462399411001840_ref54","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.4049\/jimmunol.131.6.3006","article-title":"Genetic control of the innate resistance of mice to Salmonella Typhimurium: expression of the Ity gene in peritoneal and splenic macrophages isolated in vitro","volume":"13","author":"Lissner","year":"1983","journal-title":"Journal of Immunology"},{"key":"S1462399411001840_ref36","first-page":"319","article-title":"Genetics of natural resistance to salmonellae in mice","volume":"37","author":"Hormaeche","year":"1979","journal-title":"Immunology"},{"key":"S1462399411001840_ref67","unstructured":"http:\/\/www.who.int\/mediacentre\/factsheets\/fs139\/en\/. As well as information about typhoid fever:"},{"key":"S1462399411001840_ref68","unstructured":"http:\/\/www.who.int\/vaccine_research\/diseases\/diarrhoeal\/en\/index7.html."},{"key":"S1462399411001840_ref17","first-page":"131","article-title":"The role of host cell death in Salmonella infections","volume":"289","author":"Guiney","year":"2005","journal-title":"Current Topics in Microbiology and Immunology"},{"key":"S1462399411001840_ref41","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1128\/IAI.65.2.630-635.1997","article-title":"Critical roles of neutrophils in host defense against experimental systemic infections of mice by Listeria monocytogenes, Salmonella Typhimurium, and Yersinia enterocolitica","volume":"65","author":"Conlan","year":"1997","journal-title":"Infection and Immunity"},{"key":"S1462399411001840_ref35","first-page":"311","article-title":"Natural resistance to Salmonella Typhimurium in different inbred mouse strains","volume":"37","author":"Hormaeche","year":"1979","journal-title":"Immunology"},{"key":"S1462399411001840_ref37","first-page":"329","article-title":"The natural resistance of radiation chimeras to S. Typhimurium C5","volume":"37","author":"Hormaeche","year":"1979","journal-title":"Immunology"},{"key":"S1462399411001840_ref16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0050244"}],"container-title":["Expert Reviews in Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S1462399411001840","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,10]],"date-time":"2023-06-10T14:44:16Z","timestamp":1686408256000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S1462399411001840\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,4]]},"references-count":64,"alternative-id":["S1462399411001840"],"URL":"https:\/\/doi.org\/10.1017\/s1462399411001840","relation":{},"ISSN":["1462-3994"],"issn-type":[{"value":"1462-3994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,4]]},"article-number":"e12"}}