{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:07:06Z","timestamp":1791223626575,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2005,6,4]],"date-time":"2005-06-04T00:00:00Z","timestamp":1117843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,6,15]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>The Mycobacterium tuberculosis fadD26 mutant has impaired synthesis of phthiocerol dimycocerosates (DIM) and is attenuated in BALB\/c mice. Survival analysis following direct intratracheal infection confirmed the attenuation: 60% survival at 4\u2003months post-infection versus 100% mortality at 9\u2003weeks post-infection with the wild-type strain. The fadD26 mutant induced less pneumonia and larger DTH reactions. It induced lower but progressive production of interferon (IFN)-\u03b3, interleukin (IL)-4 and tumour necrosis factor (TNF)-\u03b1. Used as a subcutaneous vaccine 60\u2003days before intratracheal challenge with a hypervirulent strain of M. tuberculosis (Beijing code 9501000), the mutant induced a higher level of protection than did Bacille Calmette\u2013Gu\u00e9rin (BCG). Seventy per cent of the mice vaccinated with the fadD26 mutant survived at 16\u2003weeks after challenge compared to 30% of those vaccinated with BCG. Similarly, there was less tissue damage (pneumonia) and lower colony-forming units (CFU) in the mice vaccinated with the fadD26 mutant compared to the findings in mice vaccinated with BCG. These data suggest that DIM synthesis is important for the pathogenicity of M. tuberculosis, and that inactivation of DIM synthesis can increase the immunogenicity of live vaccines, and increase their ability to protect against tuberculosis.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2005.02832.x","type":"journal-article","created":{"date-parts":[[2005,6,15]],"date-time":"2005-06-15T12:33:14Z","timestamp":1118838794000},"page":"21-28","source":"Crossref","is-referenced-by-count":36,"title":["Immunogenicity and protective efficacy of the <i>Mycobacterium tuberculosis fadD26<\/i> mutant"],"prefix":"10.1093","volume":"141","author":[{"given":"E","family":"Infante","sequence":"first","affiliation":[{"name":"Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition \u2018Salvador Zubir\u00e0n\u2019, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L D","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition \u2018Salvador Zubir\u00e0n\u2019, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Gicquel","sequence":"additional","affiliation":[{"name":"Unit\u00e8 de G\u00e8n\u00e8tique Mycobact\u00e8rienne, Institute Pasteur, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R Hernandez","family":"Pando","sequence":"additional","affiliation":[{"name":"Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition \u2018Salvador Zubir\u00e0n\u2019, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,6,4]]},"reference":[{"key":"2022010817004251000_b1","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1001\/jama.282.7.677","article-title":"Consensus statement: global burden of tuberculosis: estimated incidence, prevalence and mortality by country","volume":"282","author":"Dye","year":"1999","journal-title":"JAMA"},{"key":"2022010817004251000_b2","first-page":"537","article-title":"Global surveillance for antituberculosis drug resistance, 1994\u201397. World Health Organization\u2013International Union against tuberculosis and lung disease","volume":"338","author":"Pablos-Mendez","year":"1998","journal-title":"N Engl J Med"},{"key":"2022010817004251000_b3","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/S0140-6736(95)92348-9","article-title":"Variation in protection by BCG: implications for heterologous immunity","volume":"346","author":"Fine","year":"1995","journal-title":"Lancet"},{"key":"2022010817004251000_b4","doi-asserted-by":"crossref","first-page":"10965","DOI":"10.1073\/pnas.94.20.10961","article-title":"Conditionally replicating mycobacteriophages: a system for transcriptase delivery to Mycobacterium tuberculosis","volume":"94","author":"Bardarov","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022010817004251000_b5","doi-asserted-by":"crossref","first-page":"10955","DOI":"10.1073\/pnas.94.20.10955","article-title":"Efficient allelic exchange and transposon mutagenesis in Mycobacterium tuberculosis","volume":"94","author":"Pelicic","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022010817004251000_b6","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/31159","article-title":"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence","volume":"393","author":"Cole","year":"1998","journal-title":"Nature"},{"key":"2022010817004251000_b7","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1046\/j.1365-2958.1999.01593.x","article-title":"Identification of a virulence gene cluster of Mycobacterioum tuberculosis by signature tagged transposon mutagenesis","volume":"34","author":"Camacho","year":"1999","journal-title":"Mol Microbiol"},{"key":"2022010817004251000_b8","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/47042","article-title":"Complex lipid determines tissue specific replication of Mycobacterium tuberculosis in mice","volume":"402","author":"Cox","year":"1999","journal-title":"Nature"},{"key":"2022010817004251000_b9","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1128\/IAI.69.2.1442-1150.2001","article-title":"Characterization of auxotrophic mutants of Mycobacterium tuberculosis and their potential as vaccine candidates","volume":"69","author":"Smith","year":"2001","journal-title":"Infect Immun"},{"key":"2022010817004251000_b10","first-page":"2049","article-title":"Distribution of phthiocerol diester, phenolic mycosides and related compounds in mycobacteria","volume":"134","author":"Daff\u00e8","year":"1988","journal-title":"J Gen Microbiol"},{"key":"2022010817004251000_b11","doi-asserted-by":"crossref","first-page":"19845","DOI":"10.1074\/jbc.M100662200","article-title":"Analysis of the phthiocerol dimycocerosate locus of Mycobacterium tuberculosis. Evidence that this lipid is involved in the cell wall permeability","volume":"276","author":"Camacho","year":"2001","journal-title":"J Biol Chem"},{"key":"2022010817004251000_b12","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1046\/j.1462-5822.2004.00368.x","article-title":"Production of phthiocerol dimycocerosates protects Mycobacterium tuberculosis from the cidal activity of reactive nitrogen intermediates produced by macrophages and modulates the early immune response to infection","volume":"6","author":"Rousseau","year":"2004","journal-title":"Cell Microbiol"},{"key":"2022010817004251000_b13","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1126\/science.284.5419.1520","article-title":"Comparative genomics of BCG vaccines by whole-genome DNA microarray","volume":"284","author":"Behr","year":"1999","journal-title":"Science"},{"key":"2022010817004251000_b14","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1086\/380413","article-title":"Mycobacterium tuberculosis defective in phthiocerol dimycocerosate translocation provides greater protective immunity against tuberculosis than the existing bacilli Calmette\u2013Gu\u00e9rin vaccine","volume":"189","author":"Pinto","year":"2004","journal-title":"J Infect Dis"},{"key":"2022010817004251000_b15","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1046\/j.1365-2249.2003.02171.x","article-title":"A marked difference in pathogenesis and immune response induced by different Mycobacterium tuberculosis genotypes","volume":"133","author":"L\u00f2pez","year":"2003","journal-title":"Clin Exp Immunol"},{"key":"2022010817004251000_b16","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1128\/IAI.67.6.2867-2873.1999","article-title":"Persistence and protective efficacy of a Mycobacterium tuberculosis auxotroph vaccine","volume":"67","author":"Jackson","year":"1999","journal-title":"Infect Immun"},{"key":"2022010817004251000_b17","first-page":"26","article-title":"Correlation between the kinetics of Th1\/Th2 cells and pathology in a murine model of experimental pulmonary pathology","volume":"89","author":"Hern\u00e1ndez Pando","year":"1996","journal-title":"Immunology"},{"key":"2022010817004251000_b18","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1046\/j.1365-2567.1997.00193.x","article-title":"Analysis of the local kinetics and localization of interleukin 1 alpha, tumor necrosis factor alpha and transforming growth factor beta, during the course of experimental pulmonary tuberculosis","volume":"90","author":"Hern\u00e1ndez Pando","year":"1997","journal-title":"Immunology"},{"key":"2022010817004251000_b19","first-page":"84","article-title":"Pathogenesis of tuberculosis in mice exposed to low and high doses of an environmental mycobacterial saprophyte before infection","volume":"6","author":"Hern\u00e1ndez Pando","year":"1997","journal-title":"Infect Immun"},{"key":"2022010817004251000_b20","first-page":"271","article-title":"The chemistry of lipids of tubercle bacilli","volume":"35","author":"Andersen","year":"1940","journal-title":"Harvey Lect"},{"key":"2022010817004251000_b21","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/nature02384","article-title":"Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria","volume":"428","author":"Trivedl","year":"2004","journal-title":"Nature"},{"key":"2022010817004251000_b22","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1128\/iai.9.1.150-158.1974","article-title":"Lipids of putative relevance to virulence in Mycobacterium tuberculosis. Phthiocerol dimycocerosate and the attenuation indicator lipid","volume":"9","author":"Goren","year":"1974","journal-title":"Infect Immune"},{"key":"2022010817004251000_b23","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1078\/0940-2993-00182","article-title":"Expression of nitric oxide synthase and nitrotyrosine during the evolution of experimental pulmonary tuberculosis","volume":"53","author":"Hernandez-Pando","year":"2001","journal-title":"Exp Toxicol Pathol"},{"key":"2022010817004251000_b24","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1084\/jem.175.4.1111","article-title":"Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated macrophages","volume":"175","author":"Chan","year":"1992","journal-title":"J Exp Med"},{"key":"2022010817004251000_b25","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/nm868","article-title":"Building a better tuberculosis vaccine","volume":"9","author":"Young","year":"2003","journal-title":"Nat Med"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2249.2005.02832.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/141\/1\/21\/42080473\/j.1365-2249.2005.02832.x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/141\/1\/21\/42080473\/j.1365-2249.2005.02832.x.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T17:09:30Z","timestamp":1641661770000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/141\/1\/21\/6440482"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,6,4]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2005,6,4]]},"published-print":{"date-parts":[[2005,6,15]]}},"URL":"https:\/\/doi.org\/10.1111\/j.1365-2249.2005.02832.x","relation":{},"ISSN":["1365-2249","0009-9104"],"issn-type":[{"value":"1365-2249","type":"electronic"},{"value":"0009-9104","type":"print"}],"subject":[],"published-other":{"date-parts":[[2005,7]]},"published":{"date-parts":[[2005,6,4]]}}}