{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:44:28Z","timestamp":1790822668088,"version":"4.1.0"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"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":[[2015,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Aspergillus fumigatus<\/jats:named-content>\n            is the primary etiologic agent of invasive aspergillosis (IA), a major cause of death among immunosuppressed patients. Echinocandins (e.g., caspofungin) are increasingly used as second-line therapy for IA, but their activity is only fungistatic. Heat shock protein 90 (Hsp90) was previously shown to trigger tolerance to caspofungin and the paradoxical effect (i.e., decreased efficacy of caspofungin at higher concentrations). Here, we demonstrate the key role of another molecular chaperone, Hsp70, in governing the stress response to caspofungin via Hsp90 and their cochaperone Hop\/Sti1 (StiA in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. fumigatus<\/jats:named-content>\n            ). Mutation of the StiA-interacting domain of Hsp70 (C-terminal EELD motif) impaired thermal adaptation and caspofungin tolerance with loss of the caspofungin paradoxical effect. Impaired Hsp90 function and increased susceptibility to caspofungin were also observed following pharmacologic inhibition of the C-terminal domain of Hsp70 by pifithrin-\u03bc or after\n            <jats:italic>stiA<\/jats:italic>\n            deletion, further supporting the links among Hsp70, StiA, and Hsp90 in governing caspofungin tolerance. StiA was not required for the physical interaction between Hsp70 and Hsp90 but had distinct roles in the regulation of their function in caspofungin and heat stress responses. In conclusion, this study deciphering the physical and functional interactions of the Hsp70-StiA-Hsp90 complex provided new insights into the mechanisms of tolerance to caspofungin in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. fumigatus<\/jats:named-content>\n            and revealed a key C-terminal motif of Hsp70, which can be targeted by specific inhibitors, such as pifithrin-\u03bc, to enhance the antifungal activity of caspofungin against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. fumigatus<\/jats:named-content>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.00946-15","type":"journal-article","created":{"date-parts":[[2015,5,27]],"date-time":"2015-05-27T15:24:53Z","timestamp":1432740293000},"page":"4727-4733","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["Hsp70 and the Cochaperone StiA (Hop) Orchestrate Hsp90-Mediated Caspofungin Tolerance in Aspergillus fumigatus"],"prefix":"10.1128","volume":"59","author":[{"given":"Fr\u00e9d\u00e9ric","family":"Lamoth","sequence":"first","affiliation":[{"name":"Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA"},{"name":"Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland"},{"name":"Institute of Microbiology, Lausanne University Hospital, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen R.","family":"Juvvadi","sequence":"additional","affiliation":[{"name":"Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik J.","family":"Soderblom","sequence":"additional","affiliation":[{"name":"Duke Proteomics and Metabolomics Core Facility, Duke Center for Genomic and Computational Biology, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Arthur","family":"Moseley","sequence":"additional","affiliation":[{"name":"Duke Proteomics and Metabolomics Core Facility, Duke Center for Genomic and Computational Biology, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Steinbach","sequence":"additional","affiliation":[{"name":"Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA"},{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2012.08.003"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000005"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00854-09"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01154-08"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e3282f1be7f"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/424465"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1118370"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00032-12"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit530"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000532"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01857-12"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/128_2012_356"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2941"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.7.7.2568-2577.1987"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90269-I"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05164-14"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/gbe\/evt192"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1379\/1466-1268(1998)003<0118:DIOPAT>2.3.CO;2"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80830-2"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.52.35194"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.37"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.472"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.405"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.5.1.207-211.2006"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00336-08"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/157.2.591"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.01.020"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.09.023"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2012.03848.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02286-13"},{"key":"e_1_3_3_32_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1042\/bse0400041","article-title":"Role of molecular chaperones in steroid receptor action","volume":"40","author":"Pratt WB","year":"2004","unstructured":"Pratt WB, Galigniana MD, Morishima Y, Murphy PJ. 2004. 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