{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:25:47Z","timestamp":1791959147941,"version":"4.3.4"},"reference-count":63,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T00:00:00Z","timestamp":1391212800000},"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":[[2014,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n                    is a human fungal pathogen that often causes lung and brain infections in immunocompromised patients, with a high fatality rate. Our previous results showed that an F-box protein, Fbp1, is essential for\n                    <jats:named-content content-type=\"genus-species\">Cryptococcus<\/jats:named-content>\n                    virulence independent of the classical virulence factors, suggesting a novel virulence control mechanism. In this study, we show that Fbp1 is part of the ubiquitin-proteasome system, and we further investigated the mechanism of Fbp1 function during infection. Time course studies revealed that the\n                    <jats:italic>fbp1<\/jats:italic>\n                    \u0394 mutant causes little damage in the infected lung and that the fungal burden in the lung remains at a low but persistent level throughout infection. The\n                    <jats:italic>fbp1<\/jats:italic>\n                    \u0394 mutant cannot disseminate to other organs following pulmonary infection in the murine inhalation model of cryptococcosis but still causes brain infection in a murine intravenous injection model, suggesting that the block of dissemination of the\n                    <jats:italic>fbp1<\/jats:italic>\n                    \u0394 mutant is due to its inability to leave the lung. The\n                    <jats:italic>fbp1<\/jats:italic>\n                    \u0394 mutant showed a defect in intracellular proliferation after phagocytosis in a\n                    <jats:named-content content-type=\"genus-species\">Cryptococcus<\/jats:named-content>\n                    -macrophage interaction assay, which likely contributes to its virulence attenuation. To elucidate the molecular basis of the SCF(Fbp1) E3 ligase function, we analyzed potential Fbp1 substrates based on proteomic approaches combined with phenotypic analysis. One substrate, the inositol phosphosphingolipid-phospholipase C1 (Isc1), is required for fungal survival inside macrophage cells, which is consistent with the role of Fbp1 in regulating\n                    <jats:named-content content-type=\"genus-species\">Cryptococcus<\/jats:named-content>\n                    -macrophage interaction and fungal virulence. Our results thus reveal a new determinant of fungal virulence that involves the posttranslational regulation of inositol sphingolipid biosynthesis.\n                  <\/jats:p>","DOI":"10.1128\/iai.00994-13","type":"journal-article","created":{"date-parts":[[2013,11,19]],"date-time":"2013-11-19T00:01:25Z","timestamp":1384819285000},"page":"557-568","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":52,"title":["Fbp1-Mediated Ubiquitin-Proteasome Pathway Controls Cryptococcus neoformans Virulence by Regulating Fungal Intracellular Growth in Macrophages"],"prefix":"10.1128","volume":"82","author":[{"given":"Tong-Bao","family":"Liu","sequence":"first","affiliation":[{"name":"Public Health Research Institute, Rutgers University, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyang","family":"Xue","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, 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