{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:25:29Z","timestamp":1791404729076,"version":"4.3.3"},"reference-count":20,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,11,26]]},"abstract":"<jats:p>\n                    We have investigated the effect of sequence-specific antisense phosphorothioate-modified oligodeoxyribonucleotides (PS-ODNs) targeting different regions of each of the 30\/32-kDa protein complex (antigen 85 complex) encoding genes on the multiplication of\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    . Single PS-ODNs to one of the three mycolyl transferase transcripts, added either once or weekly over the 6-wk observation period, inhibited bacterial growth by up to 1 log unit. A combination of three PS-ODNs specifically targeting all three transcripts inhibited bacterial growth by \u22482 logs; the addition of these PS-ODNs weekly for 6 wk was somewhat more effective than a one-time addition. Targeting the 5\u2032 end of the transcripts was more inhibitory than targeting internal sites; the most effective PS-ODNs and target sites had minimal or no secondary structure. The effect of the PS-ODNs was specific, as mismatched PS-ODNs had little or no inhibitory activity. The antisense PS-ODNs, which were highly stable in\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    cultures, specifically blocked protein expression by their gene target. PS-ODNs targeting the transcript of a related 24-kDa protein (mpt51) had little inhibitory effect by themselves and did not increase the effect of PS-ODNs against the three members of the 30\/32-kDa protein complex. The addition of PS-ODNs against the transcripts of glutamine synthetase I (\n                    <jats:italic>gln<\/jats:italic>\n                    A1) and alanine racemase (\n                    <jats:italic>alr<\/jats:italic>\n                    ) modestly increased the inhibitory efficacy of the 30\/32-kDa protein complex-specific PS-ODNs to \u22482.5 logs. This study shows that the three mycolyl transferases are highly promising targets for antituberculous therapy by using antisense or other antimicrobial technologies.\n                  <\/jats:p>","DOI":"10.1073\/pnas.242612299","type":"journal-article","created":{"date-parts":[[2002,11,26]],"date-time":"2002-11-26T12:42:52Z","timestamp":1038314572000},"page":"15614-15619","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":54,"title":["Targeting the\n                    <i>Mycobacterium tuberculosis<\/i>\n                    30\/32-kDa mycolyl transferase complex as a therapeutic strategy against tuberculosis: Proof of principle by using antisense technology"],"prefix":"10.1073","volume":"99","author":[{"given":"G\u00fcnter","family":"Harth","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, 37-121 Center for Health Sciences, School of Medicine, University of California, 10833 Le Conte Avenue, Los Angeles, CA 90095; and Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Mail Code 1494005, Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus A.","family":"Horwitz","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, 37-121 Center for Health Sciences, School of Medicine, University of California, 10833 Le Conte Avenue, Los Angeles, CA 90095; and Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Mail Code 1494005, Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Tabatadze","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, 37-121 Center for Health Sciences, School of Medicine, University of California, 10833 Le Conte Avenue, Los Angeles, CA 90095; and Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Mail Code 1494005, Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul C.","family":"Zamecnik","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, 37-121 Center for Health Sciences, School of Medicine, University of California, 10833 Le Conte Avenue, Los Angeles, CA 90095; and Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Mail Code 1494005, Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,11,11]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199806043382301"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5317.1420"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/72413"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4461"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.8.3038-3047.1996"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118028"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.767-778.2000"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01310.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.5.1530"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.250480397"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.1.418"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/ard.1994.4.185"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(01)80842-8"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1089\/oli.1.1997.7.245"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0960-894X(96)00403-9"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1089\/oli.1.1998.8.135"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/31159"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.1.280"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1089\/ard.1994.4.279"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1089\/oli.1.1998.8.451"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.242612299","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T09:30:16Z","timestamp":1649842216000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.242612299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,11,11]]},"references-count":20,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2002,11,26]]}},"alternative-id":["10.1073\/pnas.242612299"],"URL":"https:\/\/doi.org\/10.1073\/pnas.242612299","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,11,11]]},"assertion":[{"value":"2002-10-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-11-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}