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In this stage\n              <jats:italic>, Mycobacterium tuberculosis<\/jats:italic>\n              resides inside the host in a dormant and antibiotic-tolerant state. Latent TB infection can also lead to multisystemic diseases because\n              <jats:italic>M. tuberculosis<\/jats:italic>\n              invades virtually all organs, including ocular tissues. Ocular tuberculosis (OTB) occurs when the dormant bacilli within the ocular tissues reactivate, originally seeded by hematogenous spread from pulmonary TB. Histological evidence suggests that retinal pigment epithelium (RPE) cells play a central role in immune privilege and in protection from antibiotic effects, making them an anatomical niche for invading\n              <jats:italic>M. tuberculosis<\/jats:italic>\n              . RPE cells exhibit high tolerance to environmental redox stresses, allowing phagocytosed\n              <jats:italic>M. tuberculosis<\/jats:italic>\n              bacilli to maintain viability in a dormant state. However, the microbiological and metabolic mechanisms determining the interaction between the RPE intracellular environment and phagocytosed\n              <jats:italic>M. tuberculosis<\/jats:italic>\n              are largely unknown. Here, liquid chromatography-mass spectrometry metabolomics were used to illuminate the metabolic state within RPE cells reprogrammed to harbor dormant\n              <jats:italic>M. tuberculosis<\/jats:italic>\n              bacilli and enhance antibiotic tolerance. Timely and accurate diagnosis as well as efficient chemotherapies are crucial in preventing the poor visual outcomes of OTB patients. Unfortunately, the efficacy of current methods is highly limited. Thus, the results will lead to propose a novel therapeutic option to synthetically kill the dormant\n              <jats:italic>M. tuberculosis<\/jats:italic>\n              inside the RPE cells by modulating the phenotypic state of\n              <jats:italic>M. tuberculosis<\/jats:italic>\n              and laying the foundation for a new, innovative regimen for treating OTB.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Understanding the metabolic environment within the retinal pigment epithelium (RPE) cells altered by infection with\n              <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n              and mycobacterial dormancy is crucial to identify new therapeutic methods to cure ocular tuberculosis. The present study showed that RPE cellular metabolism is altered to foster intracellular\n              <jats:italic>M. tuberculosis<\/jats:italic>\n              to enter into the dormant and drug-tolerant state, thereby blunting the efficacy of anti-tuberculosis chemotherapy. RPE cells serve as an anatomical niche as the cells protect invading bacilli from antibiotic treatment. LC-MS metabolomics of RPE cells after co-treatment with H\n              <jats:sub>2<\/jats:sub>\n              O\n              <jats:sub>2<\/jats:sub>\n              and\n              <jats:italic>M. tuberculosis<\/jats:italic>\n              infection showed that the intracellular environment within RPE cells is enriched with a greater level of oxidative stress. The antibiotic tolerance of intracellular\n              <jats:italic>M. tuberculosis<\/jats:italic>\n              within RPE cells can be restored by a metabolic manipulation strategy such as co-treatment of antibiotic with the most downstream glycolysis metabolite, phosphoenolpyruvate.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.00788-24","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T13:01:32Z","timestamp":1719320492000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["<i>Mycobacterium<\/i>\n            dormancy and antibiotic tolerance within the retinal pigment epithelium of ocular tuberculosis"],"prefix":"10.1128","volume":"12","author":[{"given":"Rachel","family":"Liu","sequence":"first","affiliation":[{"name":"Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua N.","family":"Dang","sequence":"additional","affiliation":[{"name":"Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhoeun","family":"Lee","sequence":"additional","affiliation":[{"name":"Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"},{"name":"School of Pharmacy, Sungkyunkwan University, Suwon, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niranjana","family":"Kesavamoorthy","sequence":"additional","affiliation":[{"name":"Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Ameri","sequence":"additional","affiliation":[{"name":"Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narsing","family":"Rao","sequence":"additional","affiliation":[{"name":"Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8774-6400","authenticated-orcid":false,"given":"Hyungjin","family":"Eoh","sequence":"additional","affiliation":[{"name":"Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"},{"name":"Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.TBTB2-0031-2016"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.02.004"},{"key":"e_1_3_4_4_2","unstructured":"Sharma SK Mohan A. 2004. 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