{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:03:36Z","timestamp":1791147816129,"version":"4.1.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2006,10,1]],"date-time":"2006-10-01T00:00:00Z","timestamp":1159660800000},"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":[[2006,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In recent years, sphingolipids have emerged as critical molecules in the regulation of microbial pathogenesis. In fungi, the synthesis of complex sphingolipids is important for the regulation of pathogenicity, but the role of sphingolipid degradation in fungal virulence is not known. Here, we isolated and characterized the inositol phosphosphingolipid-phospholipase C1 (\n            <jats:italic>ISC1<\/jats:italic>\n            ) gene from the fungal pathogen\n            <jats:italic>Cryptococcus neoformans<\/jats:italic>\n            and showed that it encodes an enzyme that metabolizes fungal inositol sphingolipids. Isc1 protects\n            <jats:italic>C. neoformans<\/jats:italic>\n            from acidic, oxidative, and nitrosative stresses, which are encountered by the fungus in the phagolysosomes of activated macrophages, through a Pma1-dependent mechanism(s). In an immunocompetent mouse model, the\n            <jats:italic>C. neoformans \u0394isc1<\/jats:italic>\n            mutant strain is almost exclusively found extracellularly and in a hyperencapsulated form, and its dissemination to the brain is remarkably reduced compared to that of control strains. Interestingly, the dissemination of the\n            <jats:italic>C. neoformans \u0394isc1<\/jats:italic>\n            strain to the brain is promptly restored in these mice when alveolar macrophages are pharmacologically depleted or when infecting an immunodeficient mouse in which macrophages are not efficiently activated. These studies suggest that Isc1 plays a key role in protecting\n            <jats:italic>C. neoformans<\/jats:italic>\n            from the intracellular environment of macrophages, whose activation is important for preventing fungal dissemination of the\n            <jats:italic>\u0394isc1<\/jats:italic>\n            strain to the central nervous system and the development of meningoencephalitis.\n          <\/jats:p>","DOI":"10.1128\/iai.00768-06","type":"journal-article","created":{"date-parts":[[2006,9,20]],"date-time":"2006-09-20T23:06:35Z","timestamp":1158793595000},"page":"5977-5988","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":101,"title":["The Cryptococcal Enzyme Inositol Phosphosphingolipid-Phospholipase C Confers Resistance to the Antifungal Effects of Macrophages and Promotes Fungal Dissemination to the Central Nervous System"],"prefix":"10.1128","volume":"74","author":[{"given":"John M.","family":"Shea","sequence":"first","affiliation":[{"name":"Departments of Biochemistry and Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talar B.","family":"Kechichian","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry and Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Luberto","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry and Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Del Poeta","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry and Molecular Biology"},{"name":"Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.203.1.155"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004380050530"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.9.5175-5180.2004"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.6.1437"},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","unstructured":"Casadevall A. and J. R. Perfect. 1998. Cryptococcus neoformans p. 381-405. ASM Press Washington D.C.","DOI":"10.1128\/9781555818241"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.175.4.1111"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62265-1"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.8.4585-4592.2000"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj1950301"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2003.10.029"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867043456188"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.7.4225-4237.2000"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R100022200"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)64849-5"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04220"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1081\/LPR-120014760"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413472200"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.107.5.e66"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M503404200"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M312995200"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.62.9.3158-3164.1996"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.11.4368-4374.1995"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.2.896-903.2006"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.2000.tb02601.x"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.7.4604"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.13.1.7598935"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI18309"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.856001"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507285200"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.4.1.202-208.2005"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.57.4.657"},{"key":"e_1_3_2_34_2","unstructured":"National Committee for Clinical Laboratory Standards. 1997. Reference method for broth dilution susceptibility testing of yeasts. Approved standard M27-A. National Committee for Clinical Laboratory Standards Wayne Pa."},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsim.2005.06.005"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27890"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.10.5027-5030.1998"},{"key":"e_1_3_2_38_2","unstructured":"Sambrook J. E. F. Fritsch and T. Maniatis. 1989. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press Cold Spring Harbor N.Y."},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007721200"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.5.3244"},{"key":"e_1_3_2_41_2","first-page":"861","volume":"23","year":"1991","unstructured":"Sigler, K., and M. Hofer. 1991. Activation of the plasma membrane H(+)-ATPase of Saccharomyces cerevisiae by addition of hydrogen peroxide. Biochem. Int.23:861-873.","journal-title":"Biochem. Int."},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.9.2349-2355.2000"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1080\/10715760100301171"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.5.1405-1411.1993"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052702799"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(94)90012-4"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-0059-9_27"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.20.9402"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1997.tb00973.x"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/136.5.1242"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1104\/pp.103.030023"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00768-06","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00768-06","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T06:10:33Z","timestamp":1646460633000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00768-06"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,10]]},"references-count":50,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2006,10]]}},"alternative-id":["10.1128\/IAI.00768-06"],"URL":"https:\/\/doi.org\/10.1128\/iai.00768-06","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,10]]},"assertion":[{"value":"2006-05-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-07-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-10-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}