{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:07:24Z","timestamp":1779192444897,"version":"3.51.4"},"posted":{"date-parts":[[2026,5,15]]},"group-title":"Microbiology","reference-count":21,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["P30AI18436 to SPN"],"award-info":[{"award-number":["P30AI18436 to SPN"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["5P20GM130555 to SPN"],"award-info":[{"award-number":["5P20GM130555 to SPN"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["5P20GM134974 to SPN"],"award-info":[{"award-number":["5P20GM134974 to SPN"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["R01AI155602 to WRB"],"award-info":[{"award-number":["R01AI155602 to WRB"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Macrophages are crucial for host defense against the pathogen. However, pathogens such as\n                  <jats:italic>Mycobacterium tuberculosis (Mtb)<\/jats:italic>\n                  have evolved mechanisms to alter macrophage physiology and exploit these cells as their primary niche.\n                  <jats:italic>Mtb<\/jats:italic>\n                  -infected macrophages upregulate several metabolic pathways including glutamine metabolism. We previously showed that inhibiting glutamine metabolism with the pleiotropic glutamine metabolism antagonist prodrug JHU083 has dual antibacterial and immunomodulatory effects in a mouse model of tuberculosis. In the present study, using single-cell RNA sequencing and LS-MS\/MS metabolomics, we showed that JHU083-mediated glutamine metabolism inhibition increased the population of interstitial macrophages in\n                  <jats:italic>Mtb<\/jats:italic>\n                  -infected lungs. JHU083 treatment also increased inflammatory signatures while lowering immunosuppressive markers on these macrophages. Metabolically, these macrophages exhibited marked depletion of complex lipids, accumulation of free fatty acids, and increased expression of transcripts associated with the \u03b2-oxidation pathway. Additionally, JHU083-treatment also improved phagocytic activity of macrophages, as measured by using fluorescent\n                  <jats:italic>E. coli<\/jats:italic>\n                  as a bait. In conclusion, JHU083-mediated glutamine metabolism inhibition metabolically reprograms macrophages, increasing both their lipid utilization as well as phagocytic activity, potentially driving their antimycobacterial activity that we had observed earlier.\n                <\/jats:p>","DOI":"10.64898\/2026.05.14.725218","type":"posted-content","created":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T03:30:17Z","timestamp":1778902217000},"source":"Crossref","is-referenced-by-count":0,"title":["Single-cell RNA sequencing reveals that host Glutamine Metabolism Inhibition Enhances Macrophage Phagocytosis of\n                  <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0569-9872","authenticated-orcid":false,"given":"Yingli","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, 71103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lesly Rodriguez","family":"Vicens","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, 71103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micheal","family":"Teve","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, 71103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9814-4157","authenticated-orcid":false,"given":"Barbara","family":"Slusher","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8734-4118","authenticated-orcid":false,"given":"William R","family":"Bishai","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4737-204X","authenticated-orcid":false,"given":"Sadiya","family":"Parveen-Nesson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, 71103, 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