{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:08:01Z","timestamp":1789967281495,"version":"4.0.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Arginine contributes to host defense by serving as a substrate for inducible nitric oxide synthase (iNOS) to produce antimicrobial nitric oxide (NO). However, how bacterial pathogens respond to host arginine metabolism remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that\n                      <jats:italic>Salmonella<\/jats:italic>\n                      Typhimurium (\n                      <jats:italic>S<\/jats:italic>\n                      . Tm) infection causes arginine accumulation in macrophages. This accumulation is associated with two concurrent mechanisms: enhanced arginine import via upregulation of the CAT2 transporter, and pathogen-mediated suppression of host iNOS expression.\n                      <jats:italic>S<\/jats:italic>\n                      . Tm then exploits this accumulated arginine as an intracellular signal to upregulate virulence gene expression and promote its replication. Mechanistically, arginine activates the type III secretion system (T3SS) encoded by\n                      <jats:italic>Salmonella<\/jats:italic>\n                      pathogenicity island 2 (SPI-2) via the bacterial transcriptional regulator ArgR, which binds to the promoter of\n                      <jats:italic>ssrA<\/jats:italic>\n                      , the key regulator of SPI-2, in an arginine-dependent manner. Disruption of\n                      <jats:italic>argR<\/jats:italic>\n                      impairs\n                      <jats:italic>S<\/jats:italic>\n                      . Tm intracellular replication and attenuates virulence in mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings reveal that\n                      <jats:italic>S<\/jats:italic>\n                      . Tm co-opts the host\u2019s arginine-mediated immune response by sensing macrophage-derived arginine as a signal to initiate its virulence program, revealing a pathogen adaptation strategy that links metabolic sensing to virulence activation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1877832","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:29:20Z","timestamp":1789964960000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Salmonella typhimurium exploits macrophage-derived arginine as an intracellular signal for SPI-2 virulence gene activation"],"prefix":"10.3389","volume":"16","author":[{"given":"Xinyue","family":"Wang","sequence":"first","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University","place":["Tianjin, China"]},{"name":"School of Synthetic Biology and Biomanufacturing, Tianjin University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Ma","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Ye","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houliang","family":"Guo","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Wang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Yan","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyang","family":"Sun","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjie","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyan","family":"Jiang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Feng","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1084\/jem.169.3.1021","article-title":"Regulation of macrophage functions by L-arginine","volume":"169","author":"Albina","year":"1989","journal-title":"J. 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