{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:07:01Z","timestamp":1791806821109,"version":"4.3.4"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Salmonella enterica<\/jats:italic> serovar Gallinarum (<jats:italic>S<\/jats:italic>. Gallinarum) is a host-specific pathogen causing fowl typhoid, a severe systemic infection in poultry, which leads to substantial economic losses due to high morbidity and mortality in many developing countries. However, less is known about the pathogenic characteristics and mechanism of <jats:italic>S<\/jats:italic>. Gallinarum-induced systemic infection in chickens. In this study, we deleted the <jats:italic>S<\/jats:italic>. Gallinarum UDP-<jats:italic>N<\/jats:italic>-acetylglucosamine-1-phosphate transferase gene, which contributes to the biosynthesis of enterobacterial common antigen (ECA), and studied the pathogenicity of this <jats:italic>wecB<\/jats:italic>::Cm strain in a chicken model of systemic infection. The <jats:italic>wecB<\/jats:italic>::Cm mutant strain showed comparable growth but lower resistance to bile acid and nalidixic acid than the wild-type strain <jats:italic>in vitro<\/jats:italic>. In the oral infection model of chickens, the virulence of the <jats:italic>wecB<\/jats:italic>::Cm strain was significantly attenuated <jats:italic>in vivo<\/jats:italic>. Chickens infected with wild-type strain showed typical clinical signs and pathological changes of fowl typhoid and died between 6 and 9 days post-infection, and the bacteria rapidly disseminated to systemic organs and increased in the livers and spleens. In contrast, the <jats:italic>wecB<\/jats:italic>::Cm mutant strain did not cause chicken death, there were no significant clinical changes, and the bacterial numbers in the liver and spleen of the chickens were significantly lower than those of the chickens infected with the wild-type strain. In addition, the expression of interleukin (IL)-1\u03b2, tumor necrosis factor (TNF)-\u03b1, and CXCLi1 in the livers of <jats:italic>wecB<\/jats:italic>::Cm-infected chickens was significantly lower than that of the chickens infected with the wild-type strain. Furthermore, the attenuated <jats:italic>wecB<\/jats:italic>::Cm strain could persistently colonize the liver and spleen at low levels for up to 25 days post-infection and could induce a protective immune response in the chickens. These results indicate that the <jats:italic>wecB<\/jats:italic> gene is an important virulence factor of <jats:italic>S<\/jats:italic>. Gallinarum in the chicken model of systemic infection, and the avirulent <jats:italic>wecB<\/jats:italic>::Cm mutant could possibly be used as a live-attenuated vaccine strain for controlling fowl typhoid.<\/jats:p>","DOI":"10.3389\/fmicb.2022.880932","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T10:15:55Z","timestamp":1653560155000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["wecB Gene of Salmonella Gallinarum Plays a Critical Role in Systemic Infection of Fowl Typhoid"],"prefix":"10.3389","volume":"13","author":[{"given":"Shinjiro","family":"Ojima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisaya K.","family":"Ono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Okimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Sugiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Yoshioka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Haneda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Okamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Liang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"7142","DOI":"10.1016\/S0021-9258(18)48216-6","article-title":"Biosynthesis of enterobacterial common antigen in Escherichia coli. In vitro synthesis of lipid-linked intermediates","volume":"262","author":"Barr","year":"1987","journal-title":"J. Biol. Chem."},{"key":"B2","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1128\/jb.170.1.228-233.1988","article-title":"Characterization of an Escherichia coli rff mutant defective in transfer of N-acetylmannosaminuronic acid (ManNAcA) from UDP-ManNAcA to a lipid-linked intermediate involved in enterobacterial common antigen synthesis","volume":"170","author":"Barr","year":"1988","journal-title":"J. Bacteriol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/03079457.2010.542575","article-title":"Pullorum disease and fowl typhoid\u2013new thoughts on old diseases: a review","volume":"40","author":"Barrow","year":"2011","journal-title":"Avian Pathol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1046\/j.1365-2958.2002.02768.x","article-title":"Involvement of surface polysaccharides in the organic acid resistance of Shiga Toxin-producing Escherichia coli O157: H7","volume":"43","author":"Barua","year":"2002","journal-title":"Mol. Microbiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1126\/science.277.5331.1453","article-title":"The complete genome sequence of Escherichia coli K-12","volume":"277","author":"Blattner","year":"1997","journal-title":"Science"},{"key":"B6","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1111\/mmi.13936","article-title":"Genes affecting progression of bacteriophage P22 infection in Salmonella identified by transposon and single gene deletion screens","volume":"108","author":"Bohm","year":"2018","journal-title":"Mol. Microbiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/j.ijmm.2015.05.004","article-title":"An enterobacterial common antigen mutant of Salmonella enterica serovar Typhimurium as a vaccine candidate","volume":"305","author":"Bridge","year":"2015","journal-title":"Int. J. Med. Microbiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"14993","DOI":"10.1021\/bi001627x","article-title":"The structure of UDP-N-acetylglucosamine 2-epimerase reveals homology to phosphoglycosyl transferases","volume":"39","author":"Campbell","year":"2000","journal-title":"Biochemistry"},{"key":"B9","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1128\/JB.01348-07","article-title":"Enterobacterial common antigen integrity is a checkpoint for flagellar biogenesis in Serratia marcescens","volume":"190","author":"Castelli","year":"2008","journal-title":"J. Bacteriol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1128\/JB.00839-10","article-title":"The Rcs signal transduction pathway is triggered by enterobacterial common antigen structure alterations in Serratia marcescens","volume":"193","author":"Castelli","year":"2011","journal-title":"J. Bacteriol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"6640","DOI":"10.1073\/pnas.120163297","article-title":"One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products","volume":"97","author":"Datsenko","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B12","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1128\/MMBR.00015-13","article-title":"Salmonella pathogenicity and host adaptation in chicken-associated serovars","volume":"77","author":"Foley","year":"2013","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.3390\/pathogens10101299","article-title":"Revisiting persistent Salmonella infection and the carrier state: what do we know?","volume":"10","author":"Foster","year":"2021","journal-title":"Pathogens"},{"key":"B14","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1128\/IAI.05559-11","article-title":"Enterobacterial common antigen mutants of Salmonella enterica serovar Typhimurium establish a persistent infection and provide protection against subsequent lethal challenge","volume":"80","author":"Gilbreath","year":"2012","journal-title":"Infect. Immun."},{"key":"B15","doi-asserted-by":"publisher","first-page":"4285","DOI":"10.1016\/j.vaccine.2016.07.010","article-title":"Regulated delayed synthesis of lipopolysaccharide and enterobacterial common antigen of Salmonella Typhimurium enhances immunogenicity and cross-protective efficacy against heterologous Salmonella challenge","volume":"34","author":"Huang","year":"2016","journal-title":"Vaccine"},{"key":"B16","doi-asserted-by":"publisher","first-page":"420","DOI":"10.3389\/fcimb.2019.00420","article-title":"Dynamics and outcome of macrophage interaction between Salmonella Gallinarum, Salmonella Typhimurium, and Salmonella Dublin and macrophages from chicken and cattle","volume":"9","author":"Huang","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e00552","DOI":"10.1128\/IAI.00552-19","article-title":"Interaction differences of the avian host-specific Salmonella enterica serovar Gallinarum, the host-generalist S. Typhimurium, and the cattle host-adapted S. Dublin with chicken primary macrophage","volume":"87","author":"Huang","year":"2019","journal-title":"Infect. Immun."},{"key":"B18","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s13099-015-0070-4","article-title":"The O-antigen negative \u0394wbaV mutant of Salmonella enterica serovar Enteritidis shows adaptive resistance to antimicrobial peptides and elicits colitis in streptomycin pretreated mouse model","volume":"7","author":"Jaiswal","year":"2015","journal-title":"Gut Pathog."},{"key":"B19","first-page":"717556","article-title":"Radiation-inactivated S. Gallinarum vaccine provides a high protective immune response by activating both humoral and cellular immunity","volume-title":"Front. Immunol","author":"Ji","year":"2021"},{"key":"B20","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1111\/mmi.14590","article-title":"Mutations in enterobacterial common antigen biosynthesis restore outer membrane barrier function in Escherichia coli tol-pal mutants","volume":"114","author":"Jiang","year":"2020","journal-title":"Mol. Microbiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/mmi.13284","article-title":"Dead \u2013 end intermediates in the enterobacterial common antigen biosynthesis restore outer membrane barrier functio Escherichia coli by competing for undecaprenyl phosphate","volume":"100","author":"Jorgenson","year":"2016","journal-title":"Mol. Microbiol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"8457","DOI":"10.1016\/S0021-9258(19)86913-2","article-title":"Enzymatic synthesis of uridine diphosphate N-acetyl-D-mannosaminuronic acid","volume":"254","author":"Kawamura","year":"1979","journal-title":"J. Biol. Chem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.vetmic.2019.05.019","article-title":"Molecular evolution of Salmonella enterica subsp. enterica serovar Gallinarum biovar Gallinarum in the field","volume":"235","author":"Kim","year":"2019","journal-title":"Vet. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1016\/j.vaccine.2010.11.067","article-title":"Pathogenicity of SG 9R, a rough vaccine strain against fowl typhoid","volume":"29","author":"Kwon","year":"2011","journal-title":"Vaccine"},{"key":"B25","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s12866-020-01837-0","article-title":"Effect of deletion of gene cluster involved in synthesis of enterobacterial common antigen on virulence and immunogenicity of live attenuated Salmonella vaccine when delivering heterologous Streptococcus pneumoniae antigen PspA","volume":"20","author":"Liu","year":"2020","journal-title":"BMC Microbiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1023\/A:1015226507721","article-title":"Comparative pathogenesis of experimental infections with Salmonella gallinarum in local and commercial chickens","volume":"34","author":"Mdegela","year":"2002","journal-title":"Trop. Anim. Health. Prod."},{"key":"B27","doi-asserted-by":"publisher","first-page":"13490","DOI":"10.1016\/S0021-9258(18)77373-0","article-title":"Biosynthesis of enterobacterial common antigen in Escherichia coli. Biochemical characterization of Tn10 insertion mutants defective in enterobacterial common antigen synthesis","volume":"265","author":"Meier-Dieter","year":"1990","journal-title":"J. Biol. Chem."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e01321","DOI":"10.1128\/mBio.01321-18","article-title":"Cyclic enterobacterial common antigen maintains the outer membrane permeability barrier of Escherichia coli in a manner controlled by YhdP","volume":"9","author":"Mitchell","year":"2018","journal-title":"mBio"},{"key":"B29","doi-asserted-by":"publisher","first-page":"10269","DOI":"10.1021\/ja971718q","article-title":"Eliminations in the reactions catalyzed by UDP-N-acetylglucosamine 2-epimerase","volume":"119","author":"Morgan","year":"1997","journal-title":"J. Am. Chem. Soc."},{"key":"B30","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.cell.2010.11.052","article-title":"Phenotypic landscape of a bacterial cell","volume":"144","author":"Nichols","year":"2011","journal-title":"Cell"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1292\/jvms.21-0227","article-title":"Characteristics of systemic infection and host responses in chickens experimentally infected with Salmonella enterica serovar Gallinarum biovar Gallinarum","volume":"83","author":"Ojima","year":"2021","journal-title":"J. Vet. Med. Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2853","DOI":"10.1016\/j.vaccine.2010.01.058","article-title":"Control of Salmonella Enteritidis and Salmonella Gallinarum in birds by using live vaccine candidate containing attenuated Salmonella Gallinarum mutant strain","volume":"28","author":"Penha Filho","year":"2010","journal-title":"Vaccine"},{"key":"B33","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.rvsc.2016.06.011","article-title":"Evaluation of protective immune response against fowl typhoid in chickens vaccinated with the attenuated strain Salmonella Gallinarum \u0394cobS\u0394cbiA","volume":"107","author":"Penha Filho","year":"2016","journal-title":"Res. Vet. Sci"},{"key":"B34","doi-asserted-by":"publisher","first-page":"e0284621","DOI":"10.1128\/mBio.02846-21","article-title":"ElyC and cyclic enterobacterial common antigen regulate synthesis of phosphoglyceride-linked enterobacterial common antigen","volume":"12","author":"Rai","year":"2021","journal-title":"mBio."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e01914","DOI":"10.1128\/mBio.01914-20","article-title":"Enterobacterial common antigen: synthesis and function of an enigmatic molecule","volume":"11","author":"Rai","year":"2020","journal-title":"mBio."},{"key":"B36","doi-asserted-by":"publisher","first-page":"5328","DOI":"10.1128\/JB.185.17.5328-5332.2003","article-title":"Role for Salmonella enterica enterobacterial common antigen in bile resistance and virulence","volume":"185","author":"Ramos-Morales","year":"2003","journal-title":"J. Bacteriol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1128\/jb.162.2.494-503.1985","article-title":"Biosynthesis of enterobacterial common antigen","volume":"162","author":"Rick","year":"1985","journal-title":"J. Bacteriol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1093\/glycob\/8.6.557","article-title":"Characterization of the lipid-carrier involved in the synthesis of enterobacterial common antigen (ECA) and identification of a novel phosphoglyceride in a mutant of Salmonella typhimurium defective in ECA synthesis","volume":"8","author":"Rick","year":"1998","journal-title":"Glycobiology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1038\/s41586-018-0344-3","article-title":"The outer membrane is an essential load-bearing element in Gram-negative bacteria","volume":"559","author":"Rojas","year":"2018","journal-title":"Nature"},{"key":"B40","doi-asserted-by":"publisher","first-page":"3033","DOI":"10.1021\/ja960266z","article-title":"Enzymatic formation and release of a stable glycal intermediate: the mechanism of the reaction catalyzed by UDP-N-acetylglucosamine 2-epimerase","volume":"118","author":"Sala","year":"1996","journal-title":"J. Am. Chem. Soc."},{"key":"B41","doi-asserted-by":"publisher","first-page":"405","DOI":"10.20506\/rst.19.2.1222","article-title":"Fowl typhoid and pullorum disease","volume":"19","author":"Shivaprasad","year":"2000","journal-title":"Rev. Sci. Tech"},{"key":"B42","first-page":"620","article-title":"\u201cPullorum Disease and Fowl Typhoid,\u201d","volume-title":"Diseases of Poultry","author":"Shivaprasad","year":"2008"},{"key":"B43","doi-asserted-by":"publisher","first-page":"701","DOI":"10.3382\/ps.0350701","article-title":"The susceptibility of different breeds of chickens to experimental Salmonella gallinarum infection","volume":"35","author":"Smith","year":"1956","journal-title":"Poult. Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.vetimm.2015.03.008","article-title":"Relationship of Salmonella infection and inflammatory intestinal response with hematological and serum biochemical values in laying hens","volume":"165","author":"Soria","year":"2015","journal-title":"Vet. Immunol. Immunopathol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"5981","DOI":"10.1128\/JB.01982-07","article-title":"Determination of antibiotic hypersensitivity among 4,000 single-gene-knockout mutants of Escherichia coli","volume":"190","author":"Tamae","year":"2008","journal-title":"J. Bacteriol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e00307","DOI":"10.1128\/IAI.00307-18","article-title":"Model of persistent Salmonella infection: Salmonella enterica serovar Pullorum modulates the immune response of the chicken from a Th17-type response towards a Th2-type response","volume":"86","author":"Tang","year":"2018","journal-title":"Infect. Immun."},{"key":"B47","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1046\/j.1365-2958.1997.2571614.x","article-title":"Modulation of the surface architecture of GramP. A. 2018 000 single-gene-knockout mutants of laying hens. diate: the mechanism of the reaction catalyzed by UDP","volume":"23","author":"Whitfield","year":"1997","journal-title":"Mol. Microbiol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1080\/03079457.2016.1240866","article-title":"Salmonella enterica serovar Gallinarum: addressing fundamental questions in bacteriology sixty years on from the 9R vaccine","volume":"46","author":"Wigley","year":"2017","journal-title":"Avian Pathol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.880932\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T10:16:00Z","timestamp":1653560160000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.880932\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,26]]},"references-count":48,"alternative-id":["10.3389\/fmicb.2022.880932"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2022.880932","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,26]]},"article-number":"880932"}}