{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T07:27:20Z","timestamp":1776929240020,"version":"3.51.2"},"reference-count":36,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,9,1]]},"abstract":"<jats:p>An estimated two billion persons are latently infected with Mycobacterium tuberculosis. The host factors that initiate and maintain this latent state and the mechanisms by which M. tuberculosis survives within latent lesions are compelling but unanswered questions. One such host factor may be nitric oxide (NO), a product of activated macrophages that exhibits antimycobacterial properties. Evidence for the possible significance of NO comes from murine models of tuberculosis showing progressive infection in animals unable to produce the inducible isoform of NO synthase and in animals treated with a NO synthase inhibitor. Here, we show that O2 and low, nontoxic concentrations of NO competitively modulate the expression of a 48-gene regulon, which is expressed in vivo and prepares bacilli for survival during long periods of in vitro dormancy. NO was found to reversibly inhibit aerobic respiration and growth. A heme-containing enzyme, possibly the terminal oxidase in the respiratory pathway, likely senses and integrates NO and O2 levels and signals the regulon. These data lead to a model postulating that, within granulomas, inhibition of respiration by NO production and O2 limitation constrains M. tuberculosis replication rates in persons with latent tuberculosis.<\/jats:p>","DOI":"10.1084\/jem.20030205","type":"journal-article","created":{"date-parts":[[2003,9,2]],"date-time":"2003-09-02T19:07:00Z","timestamp":1062529620000},"page":"705-713","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":827,"title":["Inhibition of Respiration by Nitric Oxide Induces a<i>Mycobacterium tuberculosis<\/i>Dormancy Program"],"prefix":"10.1084","volume":"198","author":[{"given":"Martin I.","family":"Voskuil","sequence":"first","affiliation":[{"name":"1Department of Medicine and Department of Microbiology and Immunology, Division of Infectious Diseases and Geographic Medicine, Stanford Medical School, Stanford, CA 94305"},{"name":"2Department of Microbiology, University of Colorado Health Sciences Center, Denver, CO 80262"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Schnappinger","sequence":"additional","affiliation":[{"name":"1Department of Medicine and Department of Microbiology and Immunology, Division of Infectious Diseases and Geographic Medicine, Stanford Medical School, Stanford, CA 94305"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin C.","family":"Visconti","sequence":"additional","affiliation":[{"name":"1Department of Medicine and Department of Microbiology and Immunology, Division of Infectious Diseases and Geographic Medicine, Stanford Medical School, Stanford, CA 94305"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria I.","family":"Harrell","sequence":"additional","affiliation":[{"name":"3Department of Pathobiology, University of Washington, Seattle, WA 98195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory M.","family":"Dolganov","sequence":"additional","affiliation":[{"name":"4Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA 94143"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Sherman","sequence":"additional","affiliation":[{"name":"3Department of Pathobiology, University of Washington, Seattle, WA 98195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary K.","family":"Schoolnik","sequence":"additional","affiliation":[{"name":"1Department of Medicine and Department of Microbiology and Immunology, Division of Infectious Diseases and Geographic Medicine, Stanford Medical School, Stanford, CA 94305"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2003,9,2]]},"reference":[{"key":"2023072512112069800_BIB1","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1001\/jama.282.7.677","volume":"282","year":"1999","journal-title":"JAMA."},{"key":"2023072512112069800_BIB2","doi-asserted-by":"crossref","first-page":"4195","DOI":"10.1128\/IAI.69.7.4195-4201.2001","volume":"69","year":"2001","journal-title":"Infect. 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