{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T02:24:09Z","timestamp":1781058249900,"version":"3.54.1"},"reference-count":74,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"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":[[2014,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    During infection of the mammalian host,\n                    <jats:named-content content-type=\"genus-species\">Histoplasma capsulatum<\/jats:named-content>\n                    yeasts survive and reside within macrophages of the immune system. Whereas some intracellular pathogens escape into the host cytosol,\n                    <jats:named-content content-type=\"genus-species\">Histoplasma<\/jats:named-content>\n                    yeasts remain within the macrophage phagosome. This intracellular\n                    <jats:named-content content-type=\"genus-species\">Histoplasma<\/jats:named-content>\n                    -containing compartment imposes nutritional challenges for yeast growth and replication. We identified and annotated vitamin synthesis pathways encoded in the\n                    <jats:named-content content-type=\"genus-species\">Histoplasma<\/jats:named-content>\n                    genome and confirmed by growth in minimal medium that\n                    <jats:named-content content-type=\"genus-species\">Histoplasma<\/jats:named-content>\n                    yeasts can synthesize all essential vitamins with the exception of thiamine. Riboflavin, pantothenate, and biotin auxotrophs of\n                    <jats:named-content content-type=\"genus-species\">Histoplasma<\/jats:named-content>\n                    were generated to probe whether these vitamins are available to intracellular yeasts. Disruption of the\n                    <jats:italic>RIB2<\/jats:italic>\n                    gene (riboflavin biosynthesis) prevented growth and proliferation of yeasts in macrophages and severely attenuated\n                    <jats:named-content content-type=\"genus-species\">Histoplasma<\/jats:named-content>\n                    virulence in a murine model of respiratory histoplasmosis. Rib2-deficient yeasts were not cleared from lung tissue but persisted, consistent with functional survival mechanisms but inability to replicate\n                    <jats:italic>in vivo<\/jats:italic>\n                    . In addition, depletion of Pan6 (pantothenate biosynthesis) but not Bio2 function (biotin synthesis) also impaired\n                    <jats:named-content content-type=\"genus-species\">Histoplasma<\/jats:named-content>\n                    virulence. These results indicate that the\n                    <jats:named-content content-type=\"genus-species\">Histoplasma<\/jats:named-content>\n                    -containing phagosome is limiting for riboflavin and pantothenate and that\n                    <jats:named-content content-type=\"genus-species\">Histoplasma<\/jats:named-content>\n                    virulence requires\n                    <jats:italic>de novo<\/jats:italic>\n                    synthesis of these cofactor precursors. Since mammalian hosts do not rely on vitamin synthesis but instead acquire essential vitamins through diet, vitamin synthesis pathways represent druggable targets for therapeutics.\n                  <\/jats:p>","DOI":"10.1128\/iai.00824-13","type":"journal-article","created":{"date-parts":[[2013,11,4]],"date-time":"2013-11-04T22:14:35Z","timestamp":1383603275000},"page":"393-404","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["Histoplasma capsulatum Depends on\n                    <i>De Novo<\/i>\n                    Vitamin Biosynthesis for Intraphagosomal Proliferation"],"prefix":"10.1128","volume":"82","author":[{"given":"Andrew L.","family":"Garfoot","sequence":"first","affiliation":[{"name":"Department of Microbiology, Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, 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