{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:29:18Z","timestamp":1791296958955,"version":"4.1.0"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2014,9,16]],"date-time":"2014-09-16T00:00:00Z","timestamp":1410825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,10,31]],"date-time":"2014-10-31T00:00:00Z","timestamp":1414713600000},"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":["mBio"],"published-print":{"date-parts":[[2014,10,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n            strains isolated from patients with AIDS secrete acid phosphatase, but the identity and role of the enzyme(s) responsible have not been elucidated. By combining a one-dimensional electrophoresis step with mass spectrometry, a canonically secreted acid phosphatase, CNAG_02944 (Aph1), was identified in the secretome of the highly virulent serotype A strain H99. We created an\n            <jats:italic>APH1<\/jats:italic>\n            deletion mutant (\n            <jats:italic>\u0394aph1<\/jats:italic>\n            ) and showed that\n            <jats:italic>\u0394aph1<\/jats:italic>\n            -infected\n            <jats:named-content content-type=\"genus-species\">Galleria mellonella<\/jats:named-content>\n            and mice survived longer than those infected with the wild type (WT), demonstrating that Aph1 contributes to cryptococcal virulence. Phosphate starvation induced\n            <jats:italic>APH1<\/jats:italic>\n            expression and secretion of catalytically active acid phosphatase in the WT, but not in the\n            <jats:italic>\u0394aph1<\/jats:italic>\n            mutant, indicating that Aph1 is the major extracellular acid phosphatase in\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            and that it is phosphate repressible. DsRed-tagged Aph1 was transported to the fungal cell periphery and vacuoles via endosome-like structures and was enriched in bud necks. A similar pattern of Aph1 localization was observed in cryptococci cocultured with THP-1 monocytes, suggesting that Aph1 is produced during host infection. In contrast to Aph1, but consistent with our previous biochemical data, green fluorescent protein (GFP)-tagged phospholipase B1 (Plb1) was predominantly localized at the cell periphery, with no evidence of endosome-mediated export. Despite use of different intracellular transport routes by Plb1 and Aph1, secretion of both proteins was compromised in a \u0394\n            <jats:italic>sec14-1<\/jats:italic>\n            mutant. Secretions from the WT, but not from\n            <jats:italic>\u0394aph1<\/jats:italic>\n            , hydrolyzed a range of physiological substrates, including phosphotyrosine, glucose-1-phosphate, \u03b2-glycerol phosphate, AMP, and mannose-6-phosphate, suggesting that the role of Aph1 is to recycle phosphate from macromolecules in cryptococcal vacuoles and to scavenge phosphate from the extracellular environment.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Infections with the AIDS-related fungal pathogen\n            <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n            cause more than 600,000 deaths per year worldwide. Strains of\n            <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n            isolated from patients with AIDS secrete acid phosphatase; however, the identity and role of the enzyme(s) are unknown. We have analyzed the secretome of the highly virulent serotype A strain H99 and identified Aph1, a canonically secreted acid phosphatase. By creating an\n            <jats:italic>APH1<\/jats:italic>\n            deletion mutant and an Aph1-DsRed-expressing strain, we demonstrate that Aph1 is the major extracellular and vacuolar acid phosphatase in\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            and that it is phosphate repressible. Furthermore, we show that Aph1 is produced in cryptococci during coculture with THP-1 monocytes and contributes to fungal virulence in\n            <jats:named-content content-type=\"genus-species\">Galleria mellonella<\/jats:named-content>\n            and mouse models of cryptococcosis. Our findings suggest that Aph1 is secreted to the environment to scavenge phosphate from a wide range of physiological substrates and is targeted to vacuoles to recycle phosphate from the expendable macromolecules.\n          <\/jats:p>","DOI":"10.1128\/mbio.01649-14","type":"journal-article","created":{"date-parts":[[2014,9,17]],"date-time":"2014-09-17T06:47:10Z","timestamp":1410936430000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["Identification of Aph1, a Phosphate-Regulated, Secreted, and Vacuolar Acid Phosphatase in Cryptococcus neoformans"],"prefix":"10.1128","volume":"5","author":[{"given":"Sophie","family":"Lev","sequence":"first","affiliation":[{"name":"Centre for Infectious Diseases and Microbiology, Westmead Millennium Institute and Sydney Medical School, University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Crossett","sequence":"additional","affiliation":[{"name":"School of Molecular Bioscience, University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Young","family":"Cha","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases and Microbiology, Westmead Millennium Institute and Sydney Medical School, University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desmarini","family":"Desmarini","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases and Microbiology, Westmead Millennium Institute and Sydney Medical School, University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Li","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases and Microbiology, Westmead Millennium Institute and Sydney Medical School, University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Methee","family":"Chayakulkeeree","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christabel F.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases and Microbiology, Westmead Millennium Institute and Sydney Medical School, University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. R.","family":"Williamson","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania C.","family":"Sorrell","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases and Microbiology, Westmead Millennium Institute and Sydney Medical School, University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia"},{"name":"Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julianne T.","family":"Djordjevic","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases and Microbiology, Westmead Millennium Institute and Sydney Medical School, University of Sydney at Westmead Hospital, Westmead, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02236.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20050063"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707913200"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.5.3.488-498.2006"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01351-06"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.9.5589-5596.2001"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1130-1406(06)70047-X"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2009.01644.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1567-1364.2007.00223.x"},{"key":"e_1_3_2_11_2","first-page":"3421","article-title":"Acid phosphatases of Sporothrix schenckii","volume":"132","author":"Arnold WN","year":"1986","unstructured":"ArnoldWN MannLC SakaiKH GarrisonRG ColemanPD . 1986. 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