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However, latent tuberculosis is still poorly understood, particularly because of the lack of a reliable animal model of dormant infection. Here we show that inoculation of mice with a unique streptomycin-auxotrophic mutant of<jats:italic>Mycobacterium tuberculosis<\/jats:italic>recapitulates dormant infection. The mutant grows unimpaired in the presence of streptomycin and no longer grows but remains viable for long periods of time after substrate removal, shifting from the log growth phase to the latent stage, as indicated by augmented production of \u03b1-crystallin. Mice challenged with the mutant and inoculated with streptomycin for \u223c3 weeks developed a limited infection characterized by a low bacteriological burden and the presence of typical granulomas. After substrate withdrawal, the infection was hindered but few microorganisms remained viable (dormant) in the animals' tissues for at least 6 months. In addition, the animals developed both potent T-cell responses to<jats:italic>M. tuberculosis<\/jats:italic>antigens, such as early culture filtrate, Ag85B, and ESAT-6, and resistance to reinfection with virulent<jats:italic>M. tuberculosis<\/jats:italic>. Therefore, infection of mice or other animals (e.g., guinea pigs) with<jats:italic>M. tuberculosis<\/jats:italic>strain 18b constitutes a simple and attractive animal model for evaluation of antituberculosis vaccines in the context of an<jats:italic>M. tuberculosis<\/jats:italic>-presensitized host, a prevailing condition among humans in need of a vaccine.<\/jats:p>","DOI":"10.1128\/cvi.00120-06","type":"journal-article","created":{"date-parts":[[2006,9,7]],"date-time":"2006-09-07T20:08:42Z","timestamp":1157659722000},"page":"1014-1021","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["Unique Model of Dormant Infection for Tuberculosis Vaccine Development"],"prefix":"10.1128","volume":"13","author":[{"given":"Suely S.","family":"Kashino","sequence":"first","affiliation":[{"name":"The Forsyth Institute, Boston, Massachusetts"},{"name":"Corixa Corporation, Seattle, Washington"},{"name":"Colorado State University, Fort Collins, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela","family":"Ovendale","sequence":"additional","affiliation":[{"name":"The Forsyth Institute, Boston, Massachusetts"},{"name":"Corixa Corporation, Seattle, Washington"},{"name":"Colorado State University, Fort Collins, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Izzo","sequence":"additional","affiliation":[{"name":"The Forsyth Institute, Boston, Massachusetts"},{"name":"Corixa Corporation, Seattle, Washington"},{"name":"Colorado State University, Fort Collins, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Campos-Neto","sequence":"additional","affiliation":[{"name":"The Forsyth Institute, Boston, Massachusetts"},{"name":"Corixa Corporation, Seattle, Washington"},{"name":"Colorado State University, Fort Collins, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.6.2536-2544.1994"},{"key":"e_1_3_2_3_2","first-page":"462","volume":"5","year":"2001","unstructured":"Brock, I., M. 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