{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:03:29Z","timestamp":1791266609568,"version":"4.1.0"},"reference-count":81,"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Pneumocystis<\/jats:named-content>\n pneumonia (PcP) is a significant cause of morbidity and mortality in immunocompromised patients. In humans, PcP is caused by the opportunistic fungal species\n Pneumocystis jirovecii<\/jats:named-content>\n . Progress in\n Pneumocystis<\/jats:named-content>\n research has been hampered by a lack of viable\n in vitro<\/jats:italic>\n culture methods, which limits laboratory access to human-derived organisms for drug testing. Consequently, most basic drug discovery research for\n P. jirovecii<\/jats:named-content>\n is performed using related surrogate organisms such as\n Pneumocystis carinii<\/jats:named-content>\n , which is derived from immunosuppressed rodents. While these studies provide useful insights, important questions arise about interspecies variations and the relative utility of identified anti-\n Pneumocystis<\/jats:named-content>\n agents against human\n P. jirovecii<\/jats:named-content>\n . Our recent work has identified the histone acetyltransferase (HAT) Rtt109 in\n P. carinii<\/jats:named-content>\n (i.e., PcRtt109) as a potential therapeutic target for PcP, since Rtt109 HATs are widely conserved in fungi but are absent in humans. To further address the potential utility of this target in human disease, we now demonstrate the presence of a functional Rtt109 orthologue in the clinically relevant fungal pathogen\n P. jirovecii<\/jats:named-content>\n (i.e., PjRtt109). In a fashion similar to that of\n Pcrtt109<\/jats:italic>\n ,\n Pjrtt109<\/jats:italic>\n restores H3K56 acetylation and genotoxic resistance in\n rtt109<\/jats:italic>\n -null yeast. Recombinant PjRtt109 is an active HAT\n in vitro<\/jats:italic>\n , with activity comparable to that of PcRtt109 and yeast Rtt109. PjRtt109 HAT activity is also enhanced by the histone chaperone Asf1\n in vitro<\/jats:italic>\n . PjRtt109 and PcRtt109 showed similar low micromolar sensitivities to two reported small-molecule HAT inhibitors\n in vitro<\/jats:italic>\n . Together, these results demonstrate that PjRtt109 is a functional Rtt109 HAT, and they support the development of anti-\n Pneumocystis<\/jats:named-content>\n agents directed at Rtt109-catalyzed histone acetylation as a novel therapeutic target for human PcP.\n <\/jats:p>","DOI":"10.1128\/aac.02637-14","type":"journal-article","created":{"date-parts":[[2014,4,15]],"date-time":"2014-04-15T03:30:53Z","timestamp":1397532653000},"page":"3650-3659","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Pneumocystis jirovecii Rtt109, a Novel Drug Target for Pneumocystis Pneumonia in Immunosuppressed Humans"],"prefix":"10.1128","volume":"58","author":[{"given":"Jayme L.","family":"Dahlin","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA"},{"name":"Medical Scientist Training Program, Mayo Clinic College of Medicine, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Kottom","sequence":"additional","affiliation":[{"name":"Thoracic Diseases Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota, USA"},{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhong","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Walters","sequence":"additional","affiliation":[{"name":"Institute for Therapeutics Discovery and Development, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H.","family":"Limper","sequence":"additional","affiliation":[{"name":"Thoracic Diseases Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota, USA"},{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA"},{"name":"Division of Pulmonary and Critical Care, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1513\/pats.201009-062WR"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/1753465810380102"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0b013e3282f94abc"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.112408.134335"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10156-012-0453-0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keq314"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02016-07"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.109.2.586"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc6806"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2009.117846"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1258\/ijsa.2009.008470"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.118.3.704"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.128.2.573"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2010.03318.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01554-13"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1080\/13693780400015360"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0131OC"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399405010203"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.09.116"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2009.00793.x"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1621"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1010.030994"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309984200"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1086\/314509"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1550-7408.1993.tb04902.x"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.11.4643-4647.1996"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4894(90)90089-U"},{"key":"e_1_3_2_29_2","first-page":"126S","article-title":"Establishment of Pneumocystis carinii in various mouse strains using natural transmission to initiate infection","volume":"38","author":"McFadden DC","year":"1991","unstructured":"McFaddenDCPowlesMAPittarelliLASchmatzDM. 1991. Establishment of Pneumocystis carinii in various mouse strains using natural transmission to initiate infection. J. Protozool. 38:126S\u2013127S.","journal-title":"J. Protozool."},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00967-08"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0443OC"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01173-12"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03714"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.02.006"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1133234"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1135862"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.035"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.018"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07861"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2009.119"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2175"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912427107"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078877"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2013.03.112"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm970537w"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.3544"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00126-06"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00172-13"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.2174\/138945012803530107"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0009OC"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111212200"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2005.03.002"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702496200"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.3.713-719.2000"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00428-12"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00224-13"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-224444"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi801960h"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.057794-0"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.26919-0"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.10.75"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1086\/644643"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.251579"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805813105"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2010.10.021"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1550-7408.2006.00210.x"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1550-7408.2006.00089.x"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701197200"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608025200"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M402839200"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm800657z"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2009.02.005"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm901137j"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-12-0232-T"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1021\/jf104263s"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1039\/c0fo00134a"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2007.01.016"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20540"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2012.01.017"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1080\/01635581.2012.718032"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2004.08.016"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/21.6.1183"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02637-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02637-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T22:47:17Z","timestamp":1645483637000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.02637-14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7]]},"references-count":81,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2014,7]]}},"alternative-id":["10.1128\/AAC.02637-14"],"URL":"https:\/\/doi.org\/10.1128\/aac.02637-14","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7]]},"assertion":[{"value":"2014-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-04-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-06-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}