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Recent studies in the pathobiology of\n                    <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                    identified the presence of a functioning trehalose pathway during infection and suggested its importance for\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    survival in the host. Therefore, in\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    we created null mutants of the trehalose-6-phosphate (T6P) synthase (\n                    <jats:italic>TPS1<\/jats:italic>\n                    ), trehalose-6-phophate phosphatase (\n                    <jats:italic>TPS2<\/jats:italic>\n                    ), and neutral trehalase (\n                    <jats:italic>NTH1<\/jats:italic>\n                    ) genes. We found that both\n                    <jats:italic>TPS1<\/jats:italic>\n                    and\n                    <jats:italic>TPS2<\/jats:italic>\n                    are required for high-temperature (37\u00b0C) growth and glycolysis but that the block at\n                    <jats:italic>TPS2<\/jats:italic>\n                    results in the apparent toxic accumulation of T6P, which makes this enzyme a fungicidal target. Sorbitol suppresses the growth defect in the\n                    <jats:italic>tps1<\/jats:italic>\n                    and\n                    <jats:italic>tps2<\/jats:italic>\n                    mutants at 37\u00b0C, which supports the hypothesis that these sugars (trehalose and sorbitol) act primarily as stress protectants for proteins and membranes during exposure to high temperatures in\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    . The essential nature of this pathway for disease was confirmed when a\n                    <jats:italic>tps1<\/jats:italic>\n                    mutant strain was found to be avirulent in both rabbits and mice. Furthermore, in the system of the invertebrate\n                    <jats:italic>C. elegans<\/jats:italic>\n                    , in which high in vivo temperature is no longer an environmental factor, attenuation in virulence was still noted with the\n                    <jats:italic>tps1<\/jats:italic>\n                    mutant, and this supports the hypothesis that the trehalose pathway in\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    is involved in more host survival mechanisms than simply high-temperature stresses and glycolysis. These studies in\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    and previous studies in other pathogenic fungi support the view of the trehalose pathway as a selective fungicidal target for use in antifungal development.\n                  <\/jats:p>","DOI":"10.1128\/iai.00624-06","type":"journal-article","created":{"date-parts":[[2006,9,20]],"date-time":"2006-09-20T19:06:35Z","timestamp":1158779195000},"page":"5877-5887","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":167,"title":["Characterization and Regulation of the Trehalose Synthesis Pathway and Its Importance in the Pathogenicity of\n                    <i>Cryptococcus neoformans<\/i>"],"prefix":"10.1128","volume":"74","author":[{"given":"Elizabeth Wills","family":"Petzold","sequence":"first","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Himmelreich","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases and Microbiology and Westmead Millennium Institute, University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleftherios","family":"Mylonakis","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Rude","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dena","family":"Toffaletti","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary M.","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackie L.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Perfect","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.10.5794-5802.2003"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)71531-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(87)81170-5"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.50.33311"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(93)80191-V"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.176.13.3895-3902.1994"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1996.tb02647.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/77.1.71"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1522-2594(199909)42:3<442::AID-MRM6>3.0.CO;2-Q"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1099\/13500872-141-3-679"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.1.173-180.2003"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02236.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.443-448.2000"},{"key":"e_1_3_2_15_2","first-page":"701","volume":"233","year":"2006","unstructured":"Crowe, J. 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