{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T11:04:33Z","timestamp":1788001473014,"version":"build-2784847793"},"reference-count":95,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"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":[[2014,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Nutrient acquisition and sensing are critical aspects of microbial pathogenesis. Previous transcriptional profiling indicated that the fungal pathogen\n            <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n            , which causes meningoencephalitis in immunocompromised individuals, encounters phosphate limitation during proliferation in phagocytic cells. We therefore tested the hypothesis that phosphate acquisition and polyphosphate metabolism are important for cryptococcal virulence. Deletion of the high-affinity uptake system interfered with growth on low-phosphate medium, perturbed the formation of virulence factors (capsule and melanin), reduced survival in macrophages, and attenuated virulence in a mouse model of cryptococcosis. Additionally, analysis of nutrient sensing functions for\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            revealed regulatory connections between phosphate acquisition and storage and the iron regulator Cir1, cyclic AMP (cAMP)-dependent protein kinase A (PKA), and the calcium-calmodulin-activated protein phosphatase calcineurin. Deletion of the\n            <jats:italic>VTC4<\/jats:italic>\n            gene encoding a polyphosphate polymerase blocked the ability of\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            to produce polyphosphate. The\n            <jats:italic>vtc4<\/jats:italic>\n            mutant behaved like the wild-type strain in interactions with macrophages and in the mouse infection model. However, the fungal load in the lungs was significantly increased in mice infected with\n            <jats:italic>vtc4<\/jats:italic>\n            deletion mutants. In addition, the mutant was impaired in the ability to trigger blood coagulation\n            <jats:italic>in vitro<\/jats:italic>\n            , a trait associated with polyphosphate. Overall, this study reveals that phosphate uptake in\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            is critical for virulence and that its regulation is integrated with key signaling pathways for nutrient sensing.\n          <\/jats:p>","DOI":"10.1128\/iai.01607-14","type":"journal-article","created":{"date-parts":[[2014,4,8]],"date-time":"2014-04-08T06:06:51Z","timestamp":1396937211000},"page":"2697-2712","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":69,"title":["Defects in Phosphate Acquisition and Storage Influence Virulence of Cryptococcus neoformans"],"prefix":"10.1128","volume":"82","author":[{"given":"Matthias","family":"Kretschmer","sequence":"first","affiliation":[{"name":"Michael Smith Laboratories, Department of Microbiology and Immunology, and Faculty of Land and Food Systems, University of British Columbia, Vancouver, BC, 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