{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:29:10Z","timestamp":1791296950704,"version":"4.1.0"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T00:00:00Z","timestamp":1254355200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2009,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The trehalose pathway is essential for stress tolerance and virulence in fungi. We investigated the importance of this pathway for virulence of the pathogenic yeast\n                    <jats:italic>Cryptococcus gattii<\/jats:italic>\n                    using the highly virulent Vancouver Island, Canada, outbreak strain R265. Three genes putatively involved in trehalose biosynthesis,\n                    <jats:italic>TPS1<\/jats:italic>\n                    (trehalose-6-phosphate [T6P] synthase) and\n                    <jats:italic>TPS2<\/jats:italic>\n                    (T6P phosphatase), and degradation,\n                    <jats:italic>NTH1<\/jats:italic>\n                    (neutral trehalose), were deleted in this strain, creating the R265\n                    <jats:italic>tps1<\/jats:italic>\n                    \u0394, R265\n                    <jats:italic>tps2<\/jats:italic>\n                    \u0394, and R265\n                    <jats:italic>nth1<\/jats:italic>\n                    \u0394 mutants. As in\n                    <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                    , cellular trehalose was reduced in the R265\n                    <jats:italic>tps1<\/jats:italic>\n                    \u0394 and R265\n                    <jats:italic>tps2<\/jats:italic>\n                    \u0394 mutants, which could not grow and died, respectively, at 37\u00b0C on yeast extract-peptone-dextrose agar, suggesting that T6P accumulation in R265\n                    <jats:italic>tps2<\/jats:italic>\n                    \u0394 is directly toxic. Characterizations of the cryptococcal hexokinases and trehalose mutants support their linkage to the control of glycolysis in this species. However, unlike\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    , the\n                    <jats:italic>C. gattii<\/jats:italic>\n                    R265\n                    <jats:italic>tps1<\/jats:italic>\n                    \u0394 mutant demonstrated, in addition, defects in melanin and capsule production, supporting an influence of T6P on these virulence pathways. Attenuated virulence of the R265\n                    <jats:italic>tps1<\/jats:italic>\n                    \u0394 mutant was not due solely to its 37\u00b0C growth defect, as shown in worm studies and confirmed by suppressor mutants. Furthermore, an intact trehalose pathway controls protein secretion, mating, and cell wall integrity in\n                    <jats:italic>C. gattii<\/jats:italic>\n                    . Thus, the trehalose synthesis pathway plays a central role in the virulence composites of\n                    <jats:italic>C. gattii<\/jats:italic>\n                    through multiple mechanisms. Deletion of\n                    <jats:italic>NTH1<\/jats:italic>\n                    had no effect on virulence, but inactivation of the synthesis genes,\n                    <jats:italic>TPS1<\/jats:italic>\n                    and\n                    <jats:italic>TPS2<\/jats:italic>\n                    , has profound effects on survival of\n                    <jats:italic>C. gattii<\/jats:italic>\n                    in the invertebrate and mammalian hosts. These results highlight the central importance of this pathway in the virulence composites of both pathogenic cryptococcal species.\n                  <\/jats:p>","DOI":"10.1128\/iai.00565-09","type":"journal-article","created":{"date-parts":[[2009,8,4]],"date-time":"2009-08-04T12:07:37Z","timestamp":1249387657000},"page":"4584-4596","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":103,"title":["The Trehalose Synthesis Pathway Is an Integral Part of the Virulence Composite for\n                    <i>Cryptococcus gattii<\/i>"],"prefix":"10.1128","volume":"77","author":[{"given":"Popchai","family":"Ngamskulrungroj","sequence":"first","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, North Carolina"},{"name":"Molecular Mycology Research Laboratory, Centre for Infectious Diseases and Microbiology, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Westmead, New 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Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Methee","family":"Chayakulkeeree","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, North Carolina"},{"name":"Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand"},{"name":"Fungal Pathogenesis Research Group, Centre for Infectious Diseases and Microbiology, Westmead Millennium Institute, Westmead Hospital, Westmead, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark B.","family":"Krockenberger","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Science, University of Sydney, Camperdown, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Malik","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Science, University of Sydney, Camperdown, New South Wales, 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