{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T03:02:59Z","timestamp":1781665379933,"version":"3.54.5"},"reference-count":51,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["Grant No. 32170110"],"award-info":[{"award-number":["Grant No. 32170110"]}]},{"name":"National Natural Science Foundation of China","award":["ZR2020QC006"],"award-info":[{"award-number":["ZR2020QC006"]}]},{"name":"Natural Science Foundation of Shandong Province","award":["Grant No. 32170110"],"award-info":[{"award-number":["Grant No. 32170110"]}]},{"name":"Natural Science Foundation of Shandong Province","award":["ZR2020QC006"],"award-info":[{"award-number":["ZR2020QC006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Salmonella Typhimurium is a Gram-negative intestinal pathogen that can infect humans and a variety of animals, causing gastroenteritis or serious systemic infection. Replication within host macrophages is essential for S. Typhimurium to cause systemic infection. By analyzing transcriptome data, the expression of yhjC gene, which encodes a putative regulator in S. Typhimurium, was found to be significantly up-regulated after the internalization of Salmonella by macrophages. Whether yhjC gene is involved in S. Typhimurium systemic infection and the related mechanisms were investigated in this study. The deletion of yhjC reduced the replication ability of S. Typhimurium in macrophages and decreased the colonization of S. Typhimurium in mouse systemic organs (liver and spleen), while increasing the survival rate of the infected mice, suggesting that YhjC protein promotes systemic infection by S. Typhimurium. Furthermore, by using transcriptome sequencing and RT-qPCR assay, the transcription of several virulence genes, including spvD, iroCDE and zraP, was found to be down-regulated after the deletion of yhjC. Electrophoretic mobility shift assay showed that YhjC protein can directly bind to the promoter region of spvD and zraP to promote their transcription. These findings suggest that YhjC contributes to the systemic virulence of S. Typhimurium via the regulation of multiple virulence genes and YhjC could represent a promising target to control S. Typhimurium infection.<\/jats:p>","DOI":"10.3390\/ijms24021302","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T01:30:47Z","timestamp":1673314247000},"page":"1302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The LysR-Type Transcription Regulator YhjC Promotes the Systemic Infection of Salmonella Typhimurium in Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Wanwu","family":"Li","sequence":"first","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300457, China"},{"name":"Tianjin Key Laboratory of Microbial Functional Genomics, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Ma","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300457, China"},{"name":"Tianjin Key Laboratory of Microbial Functional Genomics, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Yan","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300457, China"},{"name":"Tianjin Key Laboratory of Microbial Functional Genomics, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Wang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300457, China"},{"name":"Tianjin Key Laboratory of Microbial Functional Genomics, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8580-606X","authenticated-orcid":false,"given":"Lingyan","family":"Jiang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300457, China"},{"name":"Tianjin Key Laboratory of Microbial Functional Genomics, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1476-0711-8-15","article-title":"Non-typhoidal Salmonella bacteraemia: Epidemiology, clinical characteristics and its\u2019 association with severe immunosuppression","volume":"8","author":"Dhanoa","year":"2009","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Neupane, D., Dulal, H., and Song, J. (2021). Enteric Fever Diagnosis: Current Challenges and Future Directions. Pathogens, 10.","DOI":"10.3390\/pathogens10040410"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1038\/s41467-021-21186-4","article-title":"Salmonella Typhimurium reprograms macrophage metabolism via T3SS effector SopE2 to promote intracellular replication and virulence","volume":"12","author":"Jiang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1128\/IAI.00639-08","article-title":"Abelson Tyrosine Kinase Facilitates Salmonella enterica Serovar Typhimurium Entry into Epithelial Cells","volume":"77","author":"Ly","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"126591","DOI":"10.1016\/j.micres.2020.126591","article-title":"Salmonella secretion systems: Differential roles in pathogen-host interactions","volume":"241","author":"Bao","year":"2020","journal-title":"Microbiol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/mi.2011.2","article-title":"Development of protective immunity to Salmonella, a mucosal pathogen with a systemic agenda","volume":"4","author":"Griffin","year":"2011","journal-title":"Mucosal Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1111\/j.1574-6976.2012.00332.x","article-title":"Salmonella\u2019s long-term relationship with its host","volume":"36","author":"Ruby","year":"2012","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1046\/j.1462-5822.2001.00137.x","article-title":"Intracellular replication of Salmonella typhimurium strains in specific subsets of splenic macrophages in vivo","volume":"3","author":"Salcedo","year":"2001","journal-title":"Cell. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.1017\/S1462399411001840","article-title":"Spread of Salmonella enterica in the body during systemic infection: Unravelling host and pathogen determinants","volume":"13","author":"Mastroeni","year":"2011","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"325","DOI":"10.4161\/viru.1.4.12361","article-title":"Altering the balance between pathogen containing vacuoles and lysosomes: A lesson from Salmonella","volume":"1","author":"Lahiri","year":"2010","journal-title":"Virulence"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104846","DOI":"10.1016\/j.micpath.2021.104846","article-title":"Interactions between Salmonella and host macrophages\u2014Dissecting NF-\u03baB signaling pathway responses","volume":"154","author":"Yang","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yin, C., Liu, Z., Xian, H., Jiao, Y., Yuan, Y., Li, Y., Li, Q., and Jiao, X. (2020). AvrA Exerts Inhibition of NF-\u03baB Pathway in Its Na\u00efve Salmonella Serotype through Suppression of p-JNK and Beclin-1 Molecules. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176063"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sun, H., Kamanova, J., Lara-Tejero, M., and Gal\u00e1n, J.E. (2016). A Family of Salmonella Type III Secretion Effector Proteins Selectively Targets the NF-\u03baB Signaling Pathway to Preserve Host Homeostasis. PLOS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005484"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Rolhion, N., Furniss, R.C.D., Grabe, G., Ryan, A., Liu, M., Matthews, S.A., and Holden, D.W. (2016). Inhibition of Nuclear Transport of NF-\u0138B p65 by the Salmonella Type III Secretion System Effector SpvD. PLOS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005653"},{"key":"ref_15","first-page":"e00010","article-title":"SseK1 and SseK3 Type III Secretion System Effectors Inhibit NF-\u03baB Signaling and Necroptotic Cell Death in Salmonella-Infected Macrophages","volume":"85","author":"Matthews","year":"2017","journal-title":"Infect. Immun."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Steeb, B., Claudi, B., Burton, N.A., Tienz, P., Schmidt, A., Farhan, H., Maz\u00e9, A., and Bumann, D. (2013). Parallel Exploitation of Diverse Host Nutrients Enhances Salmonella Virulence. PLOS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003301"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/19490976.2020.1849996","article-title":"Salmonella effector SpvB aggravates dysregulation of systemic iron metabolism via modulating the hepcidin\u2212ferroportin axis","volume":"13","author":"Deng","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"eESP00342020","DOI":"10.1128\/ecosalplus.ESP-0034-2020","article-title":"Iron Transport and Metabolism in Escherichia, Shigella, and Salmonella","volume":"9","author":"Mey","year":"2021","journal-title":"EcoSal Plus"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1111\/j.1365-2958.2007.06089.x","article-title":"Biosynthesis and IroC-dependent export of the siderophore salmochelin are essential for virulence of Salmonella enterica serovar Typhimurium","volume":"67","author":"Crouch","year":"2008","journal-title":"Mol. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1126\/science.aax7898","article-title":"Host resistance factor SLC11A1 restricts Salmonella growth through magnesium deprivation","volume":"366","author":"Cunrath","year":"2019","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1111\/mmi.13439","article-title":"Acidic pH sensing in the bacterial cytoplasm is required for Salmonella virulence","volume":"101","author":"Choi","year":"2016","journal-title":"Mol. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wu, A., Tymoszuk, P., Haschka, D., Heeke, S., Dichtl, S., Petzer, V., Seifert, M., Hilbe, R., Sopper, S., and Talasz, H. (2017). Salmonella Utilizes Zinc To Subvert Antimicrobial Host Defense of Macrophages via Modulation of NF-\u03baB Signaling. Infect. Immun., 85.","DOI":"10.1128\/IAI.00418-17"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.bbrc.2015.01.058","article-title":"CysB-dependent upregulation of the Salmonella Typhimurium cysJIH operon in response to antimicrobial compounds that induce oxidative stress","volume":"458","author":"Neumann","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1111\/mmi.12500","article-title":"Regulation of Salmonella enterica pathogenicity island 1 (SPI-1) by the LysR-type regulator LeuO","volume":"91","author":"Espinosa","year":"2014","journal-title":"Mol. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1128\/JB.186.10.2909-2920.2004","article-title":"OmpR and LeuO Positively Regulate the Salmonella enterica Serovar Typhi ompS2 Porin Gene","volume":"186","author":"Puente","year":"2004","journal-title":"J. Bacteriol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s10059-010-0063-6","article-title":"A mutation in tdcA attenuates the virulence of Salmonella enterica serovar Typhimurium","volume":"29","author":"Lim","year":"2010","journal-title":"Mol. Cells"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1111\/j.1365-2958.2012.08162.x","article-title":"LeuO is a global regulator of gene expression inSalmonella entericaserovar Typhimurium","volume":"85","author":"Dillon","year":"2012","journal-title":"Mol. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"16206","DOI":"10.1038\/nmicrobiol.2016.206","article-title":"Single-cell RNA-seq ties macrophage polarization to growth rate of intracellular Salmonella","volume":"2","author":"Saliba","year":"2016","journal-title":"Nat. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"25853","DOI":"10.1074\/jbc.M116.752782","article-title":"The Salmonella Effector SpvD Is a Cysteine Hydrolase with a Serovar-specific Polymorphism Influencing Catalytic Activity, Suppression of Immune Responses, and Bacterial Virulence","volume":"291","author":"Grabe","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1042\/BJ20111639","article-title":"ZraP is a periplasmic molecular chaperone and a repressor of the zinc-responsive two-component regulator ZraSR","volume":"442","author":"Hall","year":"2012","journal-title":"Biochem. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/sj.emboj.7601983","article-title":"Peptide-assisted degradation of the Salmonella MgtC virulence factor","volume":"27","author":"Alix","year":"2008","journal-title":"EMBO J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1099\/mic.0.000947","article-title":"Novel regulators of the csgD gene encoding the master regulator of biofilm formation in Escherichia coli K-12","volume":"166","author":"Ogasawara","year":"2020","journal-title":"Microbiology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1080\/21505594.2021.1936767","article-title":"YhjC is a novel transcriptional regulator required for Shigella flexneri virulence","volume":"12","author":"Li","year":"2021","journal-title":"Virulence"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.it.2014.12.003","article-title":"Exploiting host immunity: The Salmonella paradigm","volume":"36","author":"Behnsen","year":"2015","journal-title":"Trends Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1111\/mmi.12739","article-title":"Salmonella acquires ferrous iron from haemophagocytic macrophages","volume":"93","author":"Nagy","year":"2014","journal-title":"Mol. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1099\/mic.0.27888-0","article-title":"Functions of the siderophore esterases IroD and IroE in iron-salmochelin utilization","volume":"151","author":"Zhu","year":"2005","journal-title":"Microbiology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11075","DOI":"10.1021\/ja0522027","article-title":"In Vitro Characterization of Salmochelin and Enterobactin Trilactone Hydrolases IroD, IroE, and Fes","volume":"127","author":"Lin","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.bbrc.2011.11.107","article-title":"The MgtR regulatory peptide negatively controls expression of the MgtA Mg2+ transporter in Salmonella enterica serovar Typhimurium","volume":"417","author":"Choi","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.jmb.2013.10.014","article-title":"Binding of MgtR, a Salmonella Transmembrane Regulatory Peptide, to MgtC, a Mycobacterium tuberculosis Virulence Factor: A Structural Study","volume":"426","author":"Dai","year":"2014","journal-title":"J. Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6418","DOI":"10.1128\/jb.174.20.6418-6423.1992","article-title":"Characterization of translation termination mutations in the spv operon of the Salmonella virulence plasmid pSDL2","volume":"174","author":"Roudier","year":"1992","journal-title":"J. Bacteriol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"129","DOI":"10.3389\/fmicb.2011.00129","article-title":"The Role of the spv Genes in Salmonella Pathogenesis","volume":"2","author":"Guiney","year":"2011","journal-title":"Front. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4482","DOI":"10.1128\/jb.174.13.4482-4489.1992","article-title":"Regulation of plasmid virulence gene expression in Salmonella dublin involves an unusual operon structure","volume":"174","author":"Krause","year":"1992","journal-title":"J. Bacteriol."},{"key":"ref_43","first-page":"11279","article-title":"Critical nucleotides in the interaction of a LysR-type regulator with its target promoter region","volume":"269","author":"Parsek","year":"1994","journal-title":"catBC promoter activation by CatR. J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.bbrc.2020.06.009","article-title":"Transcriptional regulation of Salmochelin glucosyltransferase by Fur in Salmonella","volume":"529","author":"Lim","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Li, W., Li, L., Yan, X., Wu, P., Zhang, T., Fan, Y., Ma, S., Wang, X., and Jiang, L. (2022). Nitrate Utilization Promotes Systemic Infection of Salmonella Typhimurium in Mice. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137220"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1080\/21505594.2020.1870331","article-title":"Downregulation of a novel flagellar synthesis regulator AsiR promotes intracellular replication and systemic pathogenicity of Salmonella Typhimurium","volume":"12","author":"Ma","year":"2021","journal-title":"Virulence"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1002\/jobm.201900315","article-title":"The LysR-type transcriptional regulator STM0030 contributes to Salmonella Typhimurium growth in macrophages and virulence in mice","volume":"59","author":"Zhang","year":"2019","journal-title":"J. Basic Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s10123-019-00110-3","article-title":"The putative transcriptional regulator STM14_3563 facilitates Salmonella Typhimurium pathogenicity by activating virulence-related genes","volume":"23","author":"Song","year":"2019","journal-title":"Int. Microbiol."},{"key":"ref_49","first-page":"e13125","article-title":"PagR mediates the precise regulation of Salmonella pathogenicity island 2 gene expression in response to magnesium and phosphate signals in Salmonella Typhimurium","volume":"22","author":"Jiang","year":"2019","journal-title":"Cell. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Zhang, H., Song, X., Wang, P., Lv, R., Ma, S., and Jiang, L. (2019). YaeB, Expressed in Response to the Acidic pH in Macrophages, Promotes Intracellular Replication and Virulence of Salmonella Typhimurium. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184339"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1385\/MB:15:1:51","article-title":"Expression and Purification of Recombinant Proteins by Fusion to Maltose-Binding Protein","volume":"15","author":"Riggs","year":"2000","journal-title":"Mol. Biotechnol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1302\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:04:40Z","timestamp":1760119480000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,9]]},"references-count":51,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24021302"],"URL":"https:\/\/doi.org\/10.3390\/ijms24021302","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,9]]}}}