{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:01:05Z","timestamp":1791482465513,"version":"4.3.4"},"reference-count":75,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["T32GM139774"],"award-info":[{"award-number":["T32GM139774"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Michael and Tana Powell"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Leptospirosis, caused by pathogenic\n                    <jats:italic>Leptospira<\/jats:italic>\n                    spp. such as\n                    <jats:italic>L. interrogans<\/jats:italic>\n                    , is a bacterial zoonosis of increasing prevalence with no consistently effective treatments in severe cases. We sought to characterize metabolic mechanisms that support\n                    <jats:italic>L. interrogans<\/jats:italic>\n                    infection, with the ultimate goal of revealing unexplored therapeutic opportunities. We first established and validated a culture medium, which we refer to as supplemented Human Plasma-Like Medium (sHPLM). sHPLM more closely resembles the physiological environment of the human host than standard culture media, such as the EMJH (Ellinghausen-McCullough-Johnson-Harris) medium typically used for\n                    <jats:italic>Leptospira<\/jats:italic>\n                    culture. We also pioneered metabolomics approaches to study sHPLM-cultured\n                    <jats:italic>Leptospira<\/jats:italic>\n                    . Specifically, we developed a liquid chromatography\/mass spectrometry (LC\/MS) workflow for both medium metabolomics and stable isotope tracing with\n                    <jats:italic>L. interrogans<\/jats:italic>\n                    cultures. The application of these technologies in\n                    <jats:italic>L. interrogans<\/jats:italic>\n                    revealed that the amino acid glutamine is a major nitrogen source among the many available in sHPLM. Subsequent growth studies in three pathogenic\n                    <jats:italic>Leptospira<\/jats:italic>\n                    strains and the nonpathogenic strain\n                    <jats:italic>L. biflexa<\/jats:italic>\n                    Patoc-1 showed robust proliferation when only glutamine-derived nitrogen was available. Further, a small-molecule inhibitor designed to target glutamine utilization, JHU-083, effectively impaired the proliferation of\n                    <jats:italic>L. interrogans<\/jats:italic>\n                    cultures. Adding glutamine to non-physiological EMJH medium also rapidly induced a short-term proliferative boost in\n                    <jats:italic>L. interrogans<\/jats:italic>\n                    and increased biofilm formation. RNA-sequencing after glutamine exposure revealed transcriptional trends for increases in biosynthesis to support these phenotypes. Although ammonium has long been thought to be the sole nitrogen source for\n                    <jats:italic>Leptospira<\/jats:italic>\n                    spp.\n                    <jats:italic>,<\/jats:italic>\n                    our results demonstrate that glutamine provides a second source of nitrogen for biosynthesis in multiple strains and may act as a metabolite signal to alter\n                    <jats:italic>L. interrogans<\/jats:italic>\n                    physiology in ways that could influence infection. This work highlights that studying\n                    <jats:italic>L. interrogans<\/jats:italic>\n                    under physiological conditions is key to understanding mechanisms supporting infection and points to nitrogen assimilation as a potential target for therapies.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014534","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:47:54Z","timestamp":1791481674000},"page":"e1014534","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glutamine from plasma-like medium fuels nitrogen metabolism and influences proliferation in Leptospira interrogans"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7135-5878","authenticated-orcid":true,"given":"Matthew H.","family":"Ward","sequence":"first","affiliation":[{"name":"Washington University in St. Louis","place":["St. Louis, Missouri, United States of America"],"department":["Department of Chemistry"]},{"name":"Washington University in St. Louis","place":["St. Louis, Missouri, United States of America"],"department":["Department of Genetics"]},{"name":"Washington University in St. Louis","place":["St. Louis, Missouri, United States of America"],"department":["Department of Medicine"]},{"name":"Center for Mass Spectrometry and Metabolic Tracing","place":["United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Scherer","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis","place":["St. Louis, Missouri, United States of America"],"department":["Department of Chemistry"]},{"name":"Washington University in St. Louis","place":["St. Louis, Missouri, United States of America"],"department":["Department of Genetics"]},{"name":"Washington University in St. Louis","place":["St. Louis, Missouri, United States of America"],"department":["Department of Medicine"]},{"name":"Center for Mass Spectrometry and Metabolic Tracing","place":["United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah P.","family":"Shriver","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis","place":["St. Louis, Missouri, United States of America"],"department":["Department of Chemistry"]},{"name":"Washington University in St. Louis","place":["St. Louis, Missouri, United States of America"],"department":["Department of Genetics"]},{"name":"Washington University in St. Louis","place":["St. Louis, Missouri, United States of America"],"department":["Department of Medicine"]},{"name":"Center for Mass Spectrometry and Metabolic Tracing","place":["United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary J.","family":"Patti","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis","place":["St. Louis, Missouri, United States of America"],"department":["Department of Chemistry"]},{"name":"Washington University in St. Louis","place":["St. Louis, Missouri, United States of America"],"department":["Department of Genetics"]},{"name":"Washington University in St. Louis","place":["St. Louis, Missouri, United States of America"],"department":["Department of Medicine"]},{"name":"Center for Mass Spectrometry and Metabolic Tracing","place":["United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"issue":"4","key":"ppat.1014534.ref001","article-title":"Impact of environment and social gradient on Leptospira infection in urban slums","volume":"2","author":"RB Reis","year":"2008","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"ppat.1014534.ref002","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1038\/s41598-020-79546-x","article-title":"The effects of flooding and 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