{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T20:59:02Z","timestamp":1788641942673,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["32170110"],"award-info":[{"award-number":["32170110"]}]},{"name":"National Natural Science Foundation of China","award":["32070133"],"award-info":[{"award-number":["32070133"]}]},{"name":"National Natural Science Foundation of China","award":["81871624"],"award-info":[{"award-number":["81871624"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Salmonella Typhimurium is an invasive enteric pathogen that causes gastroenteritis in humans and life-threatening systemic infections in mice. During infection of the intestine, S. Typhimurium can exploit nitrate as an electron acceptor to enhance its growth. However, the roles of nitrate on S. Typhimurium systemic infection are unknown. In this study, nitrate levels were found to be significantly increased in the liver and spleen of mice systemically infected by S. Typhimurium. Mutations in genes encoding nitrate transmembrane transporter (narK) or nitrate-producing flavohemoprotein (hmpA) decreased the replication of S. Typhimurium in macrophages and reduced systemic infection in vivo, suggesting that nitrate utilization promotes S. Typhimurium systemic virulence. Moreover, nitrate utilization contributes to the acidification of the S. Typhimurium cytoplasm, which can sustain the virulence of S. Typhimurium by increasing the transcription of virulence genes encoding on Salmonella pathogenicity island 2 (SPI-2). Furthermore, the growth advantage of S. Typhimurium conferred by nitrate utilization occurred only under low-oxygen conditions, and the nitrate utilization was activated by both the global regulator Fnr and the nitrate-sensing two-component system NarX-NarL. Collectively, this study revealed a novel mechanism adopted by Salmonella to interact with its host and increase its virulence.<\/jats:p>","DOI":"10.3390\/ijms23137220","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T20:47:56Z","timestamp":1656535676000},"page":"7220","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Nitrate Utilization Promotes Systemic Infection of Salmonella Typhimurium in Mice"],"prefix":"10.3390","volume":"23","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":"Linxing","family":"Li","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":"Pan","family":"Wu","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":"Tianli","family":"Zhang","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":"Yu","family":"Fan","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":"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":"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8580-606X","authenticated-orcid":false,"given":"Lingyan","family":"Jiang","sequence":"additional","affiliation":[{"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":[[2022,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1084\/jem.20031319","article-title":"Salmonella Typhimurium Persists within Macrophages in the Mesenteric Lymph Nodes of Chronically Infected Nramp1+\/+ Mice and Can Be Reactivated by IFN\u03b3 Neutralization","volume":"199","author":"Monack","year":"2004","journal-title":"J. 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