{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:38:16Z","timestamp":1791272296303,"version":"4.1.0"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2015,9,18]],"date-time":"2015-09-18T00:00:00Z","timestamp":1442534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"},{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"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":[[2015,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Treatment of\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            with echinocandins such as caspofungin inhibits the synthesis of cell wall \u03b2-1,3-glucan, which triggers a compensatory stimulation of chitin synthesis. Activation of chitin synthesis can occur in response to sub-MICs of caspofungin and to CaCl\n            <jats:sub>2<\/jats:sub>\n            and calcofluor white (CFW), agonists of the protein kinase C (PKC), and Ca\n            <jats:sup>2+<\/jats:sup>\n            -calcineurin signaling pathways.\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            mutants with the\n            <jats:italic>chs<\/jats:italic>\n            gene (encoding chitin synthase) deleted (\u0394\n            <jats:italic>Afchs<\/jats:italic>\n            ) were tested for their response to these agonists to determine the chitin synthase enzymes that were required for the compensatory upregulation of chitin synthesis. Only the \u0394\n            <jats:italic>AfchsG<\/jats:italic>\n            mutant was hypersensitive to caspofungin, and all other \u0394\n            <jats:italic>Afchs<\/jats:italic>\n            mutants tested remained capable of increasing their chitin content in response to treatment with CaCl\n            <jats:sub>2<\/jats:sub>\n            and CFW and caspofungin. The resulting increase in cell wall chitin content correlated with reduced susceptibility to caspofungin in the wild type and all \u0394\n            <jats:italic>Afchs<\/jats:italic>\n            mutants tested, with the exception of the \u0394\n            <jats:italic>AfchsG<\/jats:italic>\n            mutant, which remained sensitive to caspofungin.\n            <jats:italic>In vitro<\/jats:italic>\n            exposure to the chitin synthase inhibitor, nikkomycin Z, along with caspofungin demonstrated synergistic efficacy that was again\n            <jats:italic>Af<\/jats:italic>\n            ChsG dependent. Dynamic imaging using microfluidic perfusion chambers demonstrated that treatment with sub-MIC caspofungin resulted initially in hyphal tip lysis. However, thickened hyphae emerged that formed aberrant microcolonies in the continued presence of caspofungin. In addition, intrahyphal hyphae were formed in response to echinocandin treatment. These\n            <jats:italic>in vitro<\/jats:italic>\n            data demonstrate that\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            has the potential to survive echinocandin treatment\n            <jats:italic>in vivo<\/jats:italic>\n            by\n            <jats:italic>Af<\/jats:italic>\n            ChsG-dependent upregulation of chitin synthesis. Chitin-rich cells may, therefore, persist in human tissues and act as the focus for breakthrough infections.\n          <\/jats:p>","DOI":"10.1128\/aac.00862-15","type":"journal-article","created":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T02:24:44Z","timestamp":1436840684000},"page":"5932-5941","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":85,"title":["Caspofungin Treatment of Aspergillus fumigatus Results in ChsG-Dependent Upregulation of Chitin Synthesis and the Formation of Chitin-Rich Microcolonies"],"prefix":"10.1128","volume":"59","author":[{"given":"Louise A.","family":"Walker","sequence":"first","affiliation":[{"name":"Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keunsook K.","family":"Lee","sequence":"additional","affiliation":[{"name":"Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A.","family":"Munro","sequence":"additional","affiliation":[{"name":"Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil A. 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