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The O-antigen side chain of the lipopolysaccharide is an immunodominant antigen, can define host-pathogen interactions, and is under consideration as a vaccine target for some Gram-negative species. The composition of the O-antigen can be modified by the activity of glycosyltransferase (\n            <jats:italic>gtr<\/jats:italic>\n            ) operons acquired by horizontal gene transfer. Here we investigate the role of two\n            <jats:italic>gtr<\/jats:italic>\n            operons that we identified in the\n            <jats:italic>S<\/jats:italic>\n            . Typhi genome. Strains were engineered to express specific\n            <jats:italic>gtr<\/jats:italic>\n            operons. Full chemical analysis of the O-antigens of these strains identified\n            <jats:italic>gtr<\/jats:italic>\n            -dependent glucosylation and acetylation. The glucosylated form of the O-antigen mediated enhanced survival in human serum and decreased complement binding. A single nucleotide deviation from an epigenetic phase variation signature sequence rendered the expression of this glucosylating\n            <jats:italic>gtr<\/jats:italic>\n            operon uniform in the population. In contrast, the expression of the acetylating\n            <jats:italic>gtrC<\/jats:italic>\n            gene is controlled by epigenetic phase variation. Acetylation did not affect serum survival, but phase variation can be an immune evasion mechanism, and thus, this modification may contribute to persistence in a host. In murine immunization studies, both O-antigen modifications were generally immunodominant. Our results emphasize that natural O-antigen modifications should be taken into consideration when assessing responses to vaccines, especially O-antigen-based vaccines, and that the\n            <jats:named-content content-type=\"genus-species\">Salmonella<\/jats:named-content>\n            <jats:italic>gtr<\/jats:italic>\n            repertoire may confound the protective efficacy of broad-ranging\n            <jats:named-content content-type=\"genus-species\">Salmonella<\/jats:named-content>\n            lipopolysaccharide conjugate vaccines.\n          <\/jats:p>","DOI":"10.1128\/iai.01021-16","type":"journal-article","created":{"date-parts":[[2017,2,7]],"date-time":"2017-02-07T01:40:31Z","timestamp":1486431631000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":48,"title":["Salmonella enterica Serovar Typhi Lipopolysaccharide O-Antigen Modification Impact on Serum Resistance and Antibody Recognition"],"prefix":"10.1128","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6829-5701","authenticated-orcid":false,"given":"Erica","family":"Kintz","sequence":"first","affiliation":[{"name":"Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, York, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Heiss","sequence":"additional","affiliation":[{"name":"Complex Carbohydrate Research Center, The University of Georgia, Athens, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Black","sequence":"additional","affiliation":[{"name":"Complex Carbohydrate Research Center, The University of Georgia, Athens, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Donohue","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, York, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naj","family":"Brown","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, York, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Davies","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, York, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parastoo","family":"Azadi","sequence":"additional","affiliation":[{"name":"Complex Carbohydrate Research Center, The University of Georgia, Athens, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Baker","sequence":"additional","affiliation":[{"name":"The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam"},{"name":"Centre for Tropical Medicine, Oxford University, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Kaye","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, York, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0446-8829","authenticated-orcid":false,"given":"Marjan","family":"van der Woude","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, York, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"346","article-title":"The global burden of typhoid fever","volume":"82","author":"Crump JA","year":"2004","unstructured":"Crump JA Luby SP Mintz ED . 2004. The global burden of typhoid fever. Bull World Health Organ 82:346\u2013353.","journal-title":"Bull World Health Organ"},{"key":"e_1_3_3_3_2","first-page":"604","article-title":"Asymptomatic typhoidal bacteremia in volunteers","volume":"161","author":"Snyder MJ","year":"1963","unstructured":"Snyder MJ Hornick RB McCrumb FR Jr Morse LJ Woodward TE . 1963. Asymptomatic typhoidal bacteremia in volunteers. Antimicrob Agents Chemother (Bethesda) 161:604\u2013607.","journal-title":"Antimicrob Agents Chemother (Bethesda)"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e328356ffeb"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.4161\/hv.29054"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.9.4418-4425.2005"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01265-10"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/131.5.553"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.188.7.2735-2739.2006"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00635"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2008.056"},{"key":"e_1_3_3_12_2","volume-title":"Antigenic formulae of the Salmonella serovars","author":"Grimont PAD","year":"2007","unstructured":"Grimont PAD Weill F-X . 2007. Antigenic formulae of the Salmonella serovars, 9th ed. 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