{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T23:36:34Z","timestamp":1789688194391,"version":"4.0.1"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI173121"],"award-info":[{"award-number":["R01AI173121"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,7,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                      Typhimurium (\n                      <jats:italic toggle=\"yes\">S<\/jats:italic>\n                      . Typhimurium) is an enteric pathogen that employs a variety of mechanisms to exploit inflammation, resulting in expansion in the intestinal tract, but host factors that contribute to or counteract the luminal expansion are not well-defined. Endoplasmic reticulum (ER) stress induces inflammation and plays an important role in the pathogenesis of infectious diseases. However, little is known about the contribution of ER stress-induced inflammation during\n                      <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                      pathogenesis. Here, we demonstrate that the ER stress markers\n                      <jats:italic toggle=\"yes\">Hspa5<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Xbp1<\/jats:italic>\n                      are induced in the colon of\n                      <jats:italic toggle=\"yes\">S<\/jats:italic>\n                      . Typhimurium-infected mice, but the pro-apoptotic transcription factor\n                      <jats:italic toggle=\"yes\">Ddit3,<\/jats:italic>\n                      which encodes the protein CHOP, is significantly reduced.\n                      <jats:italic toggle=\"yes\">S<\/jats:italic>\n                      . Typhimurium-infected mice deficient for CHOP displayed a significant decrease in inflammation, colonization, dissemination, and pathology compared to littermate control mice. Preceding the differences in\n                      <jats:italic toggle=\"yes\">S<\/jats:italic>\n                      . Typhimurium colonization, a significant decrease in\n                      <jats:italic toggle=\"yes\">Nos2<\/jats:italic>\n                      gene and inducible nitric oxide (NO) synthase (iNOS) protein expression was observed. Deletion of\n                      <jats:italic toggle=\"yes\">Chop<\/jats:italic>\n                      decreased the bioavailability of nitrate in the colon, leading to a reduced fitness advantage of wild-type\n                      <jats:italic toggle=\"yes\">S<\/jats:italic>\n                      . Typhimurium over a\n                      <jats:italic toggle=\"yes\">napA narZ narG<\/jats:italic>\n                      mutant strain (deficient in nitrate respiration). CD11b\n                      <jats:sup>+<\/jats:sup>\n                      CCR2\n                      <jats:sup>+<\/jats:sup>\n                      myeloid cells, but not intestinal epithelial cells, produced iNOS, resulting in nitrate bioavailability for\n                      <jats:italic toggle=\"yes\">S<\/jats:italic>\n                      . Typhimurium to expand in the intestinal tract in a CHOP-dependent manner. Altogether, our work demonstrates that the host protein CHOP facilitates iNOS expression in CD11b\n                      <jats:sup>+<\/jats:sup>\n                      CCR2\n                      <jats:sup>+<\/jats:sup>\n                      cells, thereby contributing to luminal expansion of\n                      <jats:italic toggle=\"yes\">S<\/jats:italic>\n                      . Typhimurium via nitrate respiration.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                        Typhimurium is a gastroenteric bacterium that replicates to large numbers within the gastrointestinal (GI) tract, allowing for efficient host-to-host transmission. One strategy that allows\n                        <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                        to expand in the GI tract is via nitrate respiration that is generated during\n                        <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                        infections. The host protein CHOP is activated within the unfolded protein response (UPR), an adaptive response pathway that is activated when cells are undergoing endoplasmic reticulum (ER) stress. ER stress has been implicated in several infectious and inflammatory diseases; however, little is known about the contribution of ER stress and the UPR during\n                        <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                        infections. Our results presented here provide more insight into the role of CHOP in the production of nitrate and the subsequent growth of\n                        <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                        in the GI tract. Altogether, our research provides a better understanding of the contribution of the ER stress protein CHOP in intestinal health and disease.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01008-26","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T13:03:34Z","timestamp":1781528614000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Nitrate-mediated luminal expansion of\n                    <i>Salmonella<\/i>\n                    Typhimurium is dependent on the ER stress protein CHOP"],"prefix":"10.1128","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4859-4122","authenticated-orcid":false,"given":"Elizabeth A.","family":"Alexander","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wmf1y16","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus","place":["Aurora, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia A.","family":"Sweet","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wmf1y16","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus","place":["Aurora, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon K.","family":"Kuss-Duerkop","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wmf1y16","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus","place":["Aurora, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2122-4156","authenticated-orcid":true,"given":"Mariana X.","family":"Byndloss","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}],"name":"Vanderbilt University Medical Center, Howard Hughes Medical Institute","place":["Nashville, USA"]},{"id":[{"id":"https:\/\/ror.org\/05dq2gs74","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center","place":["Nashville, USA"]},{"id":[{"id":"https:\/\/ror.org\/05dq2gs74","id-type":"ROR","asserted-by":"publisher"}],"name":"Vanderbilt Institute of Infection, Immunology, and Inflammation, Vanderbilt University Medical Center","place":["Nashville, USA"]},{"id":[{"id":"https:\/\/ror.org\/05dq2gs74","id-type":"ROR","asserted-by":"publisher"}],"name":"Vanderbilt Digestive Disease Center, Vanderbilt University Medical Center","place":["Nashville, USA"]},{"id":[{"id":"https:\/\/ror.org\/02vm5rt34","id-type":"ROR","asserted-by":"publisher"}],"name":"Vanderbilt Microbiome Innovation Center, Vanderbilt University","place":["Nashville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamarah E.","family":"Schaberg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wmf1y16","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus","place":["Aurora, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2231-652X","authenticated-orcid":true,"given":"A. 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