{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T05:51:19Z","timestamp":1770357079210,"version":"3.49.0"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["1IO1BX001955"],"award-info":[{"award-number":["1IO1BX001955"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P\n            <jats:sub>2<\/jats:sub>\n            ] activates the yeast cell wall integrity pathway.\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida albicans<\/jats:named-content>\n            exposure to caspofungin results in the rapid redistribution of PI(4,5)P\n            <jats:sub>2<\/jats:sub>\n            and septins to plasma membrane foci and subsequent fungicidal effects. We studied\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>\n            PI(4,5)P\n            <jats:sub>2<\/jats:sub>\n            and septin dynamics and protein kinase C (PKC)-Mkc1 cell wall integrity pathway activation following exposure to caspofungin and other drugs. PI(4,5)P\n            <jats:sub>2<\/jats:sub>\n            and septins were visualized by live imaging of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>\n            cells coexpressing green fluorescent protein (GFP)-pleckstrin homology (PH) domain and red fluorescent protein-Cdc10p, respectively. PI(4,5)P\n            <jats:sub>2<\/jats:sub>\n            was also visualized in GFP-PH domain-expressing\n            <jats:italic>C. albicans mkc1<\/jats:italic>\n            mutants. Mkc1p phosphorylation was measured as a marker of PKC-Mkc1 pathway activation. Fungicidal activity was assessed using 20-h time-kill assays. Caspofungin immediately induced PI(4,5)P\n            <jats:sub>2<\/jats:sub>\n            and Cdc10p colocalization to aberrant foci, a process that was highly dynamic over 3 h. PI(4,5)P\n            <jats:sub>2<\/jats:sub>\n            levels increased in a dose-response manner at caspofungin concentrations of \u22644\u00d7 MIC and progressively decreased at concentrations of \u22658\u00d7 MIC. Caspofungin exposure resulted in broad-based mother-daughter bud necks and arrested septum-like structures, in which PI(4,5)P\n            <jats:sub>2<\/jats:sub>\n            and Cdc10 colocalized. PKC-Mkc1 pathway activation was maximal within 10 min, peaked in response to caspofungin at 4\u00d7 MIC, and declined at higher concentrations. The caspofungin-induced PI(4,5)P\n            <jats:sub>2<\/jats:sub>\n            redistribution remained apparent in\n            <jats:italic>mkc1<\/jats:italic>\n            mutants. Caspofungin exerted dose-dependent killing and paradoxical effects at \u22644\u00d7 and \u22658\u00d7 MIC, respectively. Fluconazole, amphotericin B, calcofluor white, and H\n            <jats:sub>2<\/jats:sub>\n            O\n            <jats:sub>2<\/jats:sub>\n            did not impact the PI(4,5)P\n            <jats:sub>2<\/jats:sub>\n            or Cdc10p distribution like caspofungin did. Caspofungin exerts rapid PI(4,5)P\n            <jats:sub>2<\/jats:sub>\n            -septin and PKC-Mkc1 responses that correlate with the extent of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>\n            killing, and the responses are not induced by other antifungal agents. PI(4,5)P\n            <jats:sub>2<\/jats:sub>\n            -septin regulation is crucial in early caspofungin responses and PKC-Mkc1 activation.\n          <\/jats:p>","DOI":"10.1128\/aac.02711-15","type":"journal-article","created":{"date-parts":[[2016,3,29]],"date-time":"2016-03-29T02:23:38Z","timestamp":1459218218000},"page":"3591-3600","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["Highly Dynamic and Specific Phosphatidylinositol 4,5-Bisphosphate, Septin, and Cell Wall Integrity Pathway Responses Correlate with Caspofungin Activity against Candida albicans"],"prefix":"10.1128","volume":"60","author":[{"given":"Hassan","family":"Badrane","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Hong","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelius J.","family":"Clancy","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis021"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/1469-0691.12039"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/1060028015590838"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01366-12"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00095-11"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01480-08"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2009.09.003"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00999-10"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000040"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.12.5146-5148.2005"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2007.01.015"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405589200"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST20130226"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E02-03-0158"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.139.1.75"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2010.10.002"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00112-12"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.27998-0"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2008\/018002-0"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/371168a0"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00246-08"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-144-2-411"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12302"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030092"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E10-07-0632"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000752"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020021"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002525"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.2.6.1200-1210.2003"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000532"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.28616-0"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001069"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05588.x"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00278-12"},{"key":"e_1_3_2_36_2","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1093\/clinchem\/34.8.1665","article-title":"NCCLS proposes HIV reference material specifications. 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