{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T10:32:46Z","timestamp":1775644366873,"version":"3.50.1"},"reference-count":40,"publisher":"Proceedings of the National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,4,4]]},"abstract":"<jats:p>\n                    <jats:italic>Leishmania<\/jats:italic>\n                    are protozoan parasites that replicate within mature phagolysosomes of mammalian macrophages. To define the biochemical composition of the phagosome and carbon source requirements of intracellular stages of\n                    <jats:italic>L. major<\/jats:italic>\n                    , we investigated the role and requirement for the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP).\n                    <jats:italic>L. major<\/jats:italic>\n                    FBP was constitutively expressed in both extracellular and intracellular stages and was primarily targeted to glycosomes, modified peroxisomes that also contain glycolytic enzymes. A\n                    <jats:italic>L. major FBP<\/jats:italic>\n                    -null mutant was unable to grow in the absence of hexose, and suspension in glycerol-containing medium resulted in rapid depletion of internal carbohydrate reserves.\n                    <jats:italic>L. major<\/jats:italic>\n                    \u0394\n                    <jats:italic>fbp<\/jats:italic>\n                    promastigotes were internalized by macrophages and differentiated into amastigotes but were unable to replicate in the macrophage phagolysosome. Similarly, the mutant persisted in mice but failed to generate normal lesions. The data suggest that\n                    <jats:italic>Leishmania<\/jats:italic>\n                    amastigotes reside in a glucose-poor phagosome and depend heavily on nonglucose carbon sources. Feeding experiments with [\n                    <jats:sup>13<\/jats:sup>\n                    C]fatty acids showed that fatty acids are poor gluconeogenic substrates, indicating that amino acids are the major carbon source\n                    <jats:italic>in vivo<\/jats:italic>\n                    . The need for amino acids may have forced\n                    <jats:italic>Leishmania<\/jats:italic>\n                    spp. to adapt to life in the mature phagolysosome.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0509196103","type":"journal-article","created":{"date-parts":[[2006,3,28]],"date-time":"2006-03-28T23:28:45Z","timestamp":1143588525000},"page":"5502-5507","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":135,"title":["Virulence of\n                    <i>Leishmania major<\/i>\n                    in macrophages and mice requires the gluconeogenic enzyme fructose-1,6-bisphosphatase"],"prefix":"10.1073","volume":"103","author":[{"given":"Thomas","family":"Naderer","sequence":"first","affiliation":[{"name":"*Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia; and"}]},{"given":"Miriam A.","family":"Ellis","sequence":"additional","affiliation":[{"name":"*Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia; and"}]},{"given":"M. Fleur","family":"Sernee","sequence":"additional","affiliation":[{"name":"*Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia; and"}]},{"given":"David P.","family":"De Souza","sequence":"additional","affiliation":[{"name":"*Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia; and"}]},{"given":"Joan","family":"Curtis","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia"}]},{"given":"Emanuela","family":"Handman","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia"}]},{"given":"Malcolm J.","family":"McConville","sequence":"additional","affiliation":[{"name":"*Department of Biochemistry and 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