{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:28:54Z","timestamp":1772162934916,"version":"3.50.1"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2014,11,4]],"date-time":"2014-11-04T00:00:00Z","timestamp":1415059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,12,31]],"date-time":"2014-12-31T00:00:00Z","timestamp":1419984000000},"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":[[2014,12,31]]},"abstract":"ABSTRACT<\/jats:title>\n \n In the context of deciphering the metabolic strategies of the obligate pathogenic fungi in the genus\n Pneumocystis<\/jats:italic>\n , the genomes of three species (\n P. carinii<\/jats:named-content>\n ,\n P. murina<\/jats:named-content>\n , and\n P.\u00a0jirovecii<\/jats:italic>\n ) were compared among themselves and with the free-living, phylogenetically related fission yeast (\n Schizosaccharomyces pombe<\/jats:named-content>\n ). The underrepresentation of amino acid metabolism pathways compared to those in\n S. pombe<\/jats:named-content>\n , as well as the incomplete steroid biosynthesis pathway, were confirmed for\n P. carinii<\/jats:named-content>\n and\n P.\u00a0jirovecii<\/jats:italic>\n and extended to\n P. murina<\/jats:named-content>\n . All three\n Pneumocystis<\/jats:italic>\n species showed overrepresentation of the inositol phosphate metabolism pathway compared to that in the fission yeast. In addition to those known in\n S. pombe<\/jats:named-content>\n , four genes, encoding inositol-polyphosphate multikinase (EC 2.7.1.151), inositol-pentakisphosphate 2-kinase (EC 2.7.1.158), phosphoinositide 5-phosphatase (EC 3.1.3.36), and inositol-1,4-bisphosphate 1-phosphatase (EC 3.1.3.57), were identified in the two rodent\n Pneumocystis<\/jats:italic>\n genomes,\n P. carinii<\/jats:named-content>\n and\n P. murina<\/jats:named-content>\n . The\n P.\u00a0jirovecii<\/jats:italic>\n genome appeared to contain three of these genes but lacked phosphoinositide 5-phosphatase. Notably, two genes encoding enzymes essential for\n myo-<\/jats:italic>\n inositol synthesis, inositol-1-phosphate synthase (INO1) and inositol monophosphatase (INM1), were absent from all three genomes, suggesting that\n Pneumocystis<\/jats:italic>\n species are inositol auxotrophs. In keeping with the need to acquire exogenous inositol, two genes with products homologous to fungal inositol transporters, ITR1 and ITR2, were identified in\n P. carinii<\/jats:named-content>\n and\n P. murina<\/jats:named-content>\n , while\n P.\u00a0jirovecii<\/jats:italic>\n contained only the ITR1 homolog. The ITR and inositol metabolism genes in\n P. murina<\/jats:named-content>\n and\n P. carinii<\/jats:named-content>\n were expressed during fulminant infection as determined by reverse transcriptase real-time PCR of cDNA from infected lung tissue. Supplementation of\n in vitro<\/jats:italic>\n culture with inositol yielded significant improvement of the viability of\n P. carinii<\/jats:named-content>\n for days 7 through 14.\n <\/jats:p>\n \n IMPORTANCE<\/jats:bold>\n Microbes in the genus\n Pneumocystis<\/jats:italic>\n are obligate pathogenic fungi that reside in mammalian lungs and cause\n Pneumocystis<\/jats:italic>\n pneumonia in hosts with weakened immune systems. These fungal infections are not responsive to standard antifungal therapy. A long-term\n in vitro<\/jats:italic>\n culture system is not available for these fungi, impeding the study of their biology and genetics and new drug development. Given that all genomes of the\n Pneumocystis<\/jats:italic>\n species analyzed lack the genes for inositol synthesis and contain inositol transporters,\n Pneumocystis<\/jats:italic>\n fungi, like\n S. pombe<\/jats:named-content>\n , appear to be inositol auxotrophs. Inositol is important for the pathogenesis, virulence, and mating processes in\n Candida albicans<\/jats:named-content>\n and\n Cryptococcus neoformans<\/jats:named-content>\n , suggesting similar importance within the\n Pneumocystis<\/jats:italic>\n species as well. This is the first report to (i) characterize genes in the inositol phosphate metabolism and transport pathways in\n Pneumocystis<\/jats:italic>\n species and (ii) identify inositol as a supplement that improved the viability of\n P. carinii<\/jats:named-content>\n in\n in vitro<\/jats:italic>\n culture.\n <\/jats:p>","DOI":"10.1128\/mbio.01834-14","type":"journal-article","created":{"date-parts":[[2014,11,5]],"date-time":"2014-11-05T01:17:57Z","timestamp":1415150277000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Comparative Genomics of\n Pneumocystis<\/i>\n Species Suggests the Absence of Genes for\n myo-<\/i>\n Inositol Synthesis and Reliance on Inositol Transport and Metabolism"],"prefix":"10.1128","volume":"5","author":[{"given":"Aleksey","family":"Porollo","sequence":"first","affiliation":[{"name":"Center for Autoimmune Genomics and Etiology, Division of Biomedical Informatics, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M.","family":"Sesterhenn","sequence":"additional","affiliation":[{"name":"The Veterans Affairs Medical Center, Cincinnati, Ohio, USA"},{"name":"Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret S.","family":"Collins","sequence":"additional","affiliation":[{"name":"The Veterans Affairs Medical Center, Cincinnati, Ohio, USA"},{"name":"Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey A.","family":"Welge","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neurosciences, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie T.","family":"Cushion","sequence":"additional","affiliation":[{"name":"The Veterans Affairs Medical Center, Cincinnati, Ohio, USA"},{"name":"Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200401-094OC"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-006-9250-x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.2174\/138945012803530107"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.2174\/092986709788682038"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc6806"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11745-004-1292-5"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015152"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.28.6.1385-1394.1990"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.112408.134335"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti610"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki285"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00428-12"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000423"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2334"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(00)00240-4"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.025718-0"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.26644-0"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00327-10"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002869"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002940050334"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)99146-5"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2008.03.021"},{"key":"e_1_3_2_24_2","first-page":"239","article-title":"Pneumopathies in the newborn period","volume":"20","author":"Zytkiewicz A","year":"1965","unstructured":"ZytkiewiczA CzarkowskaD PietronK PapierkowskiA . 1965. 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