{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:29:17Z","timestamp":1792621757573,"version":"4.5.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,3,20]]},"abstract":"<jats:p>\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    , the causative agent of tuberculosis, has two distinguishing characteristics: its ability to stain acid-fast and its ability to cause long-term latent infections in humans. Although this distinctive staining characteristic has often been attributed to its lipid-rich cell wall, the specific dye-retaining components were not known. Here we report that targeted deletion of\n                    <jats:italic>kasB<\/jats:italic>\n                    , one of two\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    genes encoding distinct \u03b2-ketoacyl- acyl carrier protein synthases involved in mycolic acid synthesis, results in loss of acid-fast staining. Biochemical and structural analyses revealed that the \u0394\n                    <jats:italic>kasB<\/jats:italic>\n                    mutant strain synthesized mycolates with shorter chain lengths. An additional and unexpected outcome of\n                    <jats:italic>kasB<\/jats:italic>\n                    deletion was the loss of ketomycolic acid\n                    <jats:italic>trans<\/jats:italic>\n                    -cyclopropanation and a drastic reduction in methoxymycolic acid\n                    <jats:italic>trans<\/jats:italic>\n                    -cyclopropanation, activities usually associated with the\n                    <jats:italic>trans<\/jats:italic>\n                    -cyclopropane synthase CmaA2. Although deletion of\n                    <jats:italic>kasB<\/jats:italic>\n                    also markedly altered the colony morphology and abolished classic serpentine growth (cording), the most profound effect of\n                    <jats:italic>kasB<\/jats:italic>\n                    deletion was the ability of the mutant strain to persist in infected immunocompetent mice for up to 600 days without causing disease or mortality. This long-term persistence of \u0394\n                    <jats:italic>kasB<\/jats:italic>\n                    represents a model for studying latent\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    infections and suggests that this attenuated strain may represent a valuable vaccine candidate against tuberculosis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0608654104","type":"journal-article","created":{"date-parts":[[2007,3,13]],"date-time":"2007-03-13T01:23:01Z","timestamp":1173748981000},"page":"5157-5162","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":186,"title":["Deletion of\n                    <i>kasB<\/i>\n                    in\n                    <i>Mycobacterium tuberculosis<\/i>\n                    causes loss of acid-fastness and subclinical latent tuberculosis in immunocompetent mice"],"prefix":"10.1073","volume":"104","author":[{"given":"Apoorva","family":"Bhatt","sequence":"first","affiliation":[{"name":"*Howard Hughes Medical Institute and"},{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagatoshi","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Host Defense, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiranmai","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudagar S.","family":"Gurcha","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Kremer","sequence":"additional","affiliation":[{"name":"**Laboratoire de Dynamique Mol\u00e9culaire des Interactions Membranaires, Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 5539, Universit\u00e9 de Montpellier II, 34095 Montpellier Cedex 5, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Chen","sequence":"additional","affiliation":[{"name":"*Howard Hughes Medical Institute and"},{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven 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