{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:41:53Z","timestamp":1790390513504,"version":"4.1.0"},"reference-count":61,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2010,1,1]],"date-time":"2010-01-01T00:00:00Z","timestamp":1262304000000},"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":["Eukaryot Cell"],"published-print":{"date-parts":[[2010,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The export of virulence factors, such as the capsule polysaccharide, to the cell surface is a critical aspect of the pathogenicity of\n            <jats:italic>Cryptococcus neoformans.<\/jats:italic>\n            A view of capsule export via exocytosis and extracellular vesicles is emerging, but the molecular mechanisms underlying virulence factor transport pathways remain to be established. In this study, we characterized the\n            <jats:italic>APT1<\/jats:italic>\n            gene, which encodes a predicted integral membrane P-type ATPase belonging to the type IV, Drs2 family of aminophospholipid translocases (flippases) (APTs). APTs maintain the phospholipid asymmetry that is critical in membrane fusion events for trafficking and in establishing cell polarity. Deletion of the\n            <jats:italic>APT1<\/jats:italic>\n            gene resulted in phenotypes consistent with similar roles in\n            <jats:italic>C. neoformans<\/jats:italic>\n            . These included altered actin distribution, increased sensitivity to stress conditions (oxidative and nitrosative stress) and to trafficking inhibitors, such as brefeldin A and monensin, a reduction in exported acid phosphatase activity, and hypersensitivity to the antifungal drugs amphotericin B, fluconazole, and cinnamycin. However, there was no difference in growth, capsule size, or melanin production between the wild type and the\n            <jats:italic>apt1<\/jats:italic>\n            mutant strains at either 30\u00b0C or 37\u00b0C. Despite the absence of an influence on these major virulence factors, Apt1 was required for survival during interactions with macrophages, and\n            <jats:italic>apt1<\/jats:italic>\n            mutants exhibited attenuated virulence in a mouse inhalation model of cryptococcosis. Therefore, Apt1 contributes to virulence and the stress response in\n            <jats:italic>C. neoformans<\/jats:italic>\n            through apparent functions in membrane fusion and trafficking that do not influence the deposition of major virulence factors, such as capsule and melanin, outside the cell.\n          <\/jats:p>","DOI":"10.1128\/ec.00289-09","type":"journal-article","created":{"date-parts":[[2009,12,1]],"date-time":"2009-12-01T03:33:19Z","timestamp":1259638399000},"page":"74-83","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["A Putative P-Type ATPase, Apt1, Is Involved in Stress Tolerance and Virulence in\n            <i>Cryptococcus neoformans<\/i>"],"prefix":"10.1128","volume":"9","author":[{"given":"Guanggan","family":"Hu","sequence":"first","affiliation":[{"name":"Michael Smith Laboratories, Department of Microbiology and Immunology, Faculty of Land and Food Systems, The University 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