{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:34:58Z","timestamp":1792722898073,"version":"4.5.0"},"reference-count":74,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:00:00Z","timestamp":1687910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:00:00Z","timestamp":1687910400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["1R01AI153599"],"award-info":[{"award-number":["1R01AI153599"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            To successfully induce disease,\n            <jats:italic>Candida albicans<\/jats:italic>\n            must effectively evade the host immune system. One mechanism used by\n            <jats:italic>C. albicans<\/jats:italic>\n            to achieve this is to mask immunogenic \u03b2(1,3)-glucan epitopes within its cell wall under an outer layer of mannosylated glycoproteins. Consequently, induction of \u03b2(1,3)-glucan exposure (unmasking)\n            <jats:italic>via<\/jats:italic>\n            genetic or chemical manipulation increases fungal recognition by host immune cells\n            <jats:italic>in vitro<\/jats:italic>\n            and attenuates disease during systemic infection in mice. Treatment with the echinocandin caspofungin is one of the most potent drivers of \u03b2(1,3)-glucan exposure. Several reports using murine infection models suggest a role for the immune system, and specifically host \u03b2(1,3)-glucan receptors, in mediating the efficacy of echinocandin treatment\n            <jats:italic>in vivo<\/jats:italic>\n            . However, the mechanism by which caspofungin-induced unmasking occurs is not well understood. In this report, we show that foci of unmasking co-localize with areas of increased chitin within the yeast cell wall in response to caspofungin, and that inhibition of chitin synthesis\n            <jats:italic>via<\/jats:italic>\n            nikkomycin Z attenuates caspofungin-induced \u03b2(1,3)-glucan exposure. Furthermore, we find that both the calcineurin and Mkc1 mitogen-activated protein kinase pathways work synergistically to regulate \u03b2(1,3)-glucan exposure and chitin synthesis in response to drug treatment. When either of these pathways are interrupted, it results in a bimodal population of cells containing either high or low chitin content. Importantly, increased unmasking correlates with increased chitin content within these cells. Microscopy further indicates that caspofungin-induced unmasking correlates with actively growing cells. Collectively, our work presents a model in which chitin synthesis induces unmasking within the cell wall in response to caspofungin in growing cells.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Systemic candidiasis has reported mortality rates ranging from 20% to 40%. The echinocandins, including caspofungin, are first-line antifungals used to treat systemic candidiasis. However, studies in mice have shown that echinocandin efficacy relies on both its cidal impacts on\n              <jats:italic>Candida albicans<\/jats:italic>\n              , as well as a functional immune system to successfully clear invading fungi. In addition to direct\n              <jats:italic>C. albicans<\/jats:italic>\n              killing, caspofungin increases exposure (unmasking) of immunogenic \u03b2(1,3)-glucan moieties. To evade immune detection, \u03b2(1,3)-glucan is normally masked within the\n              <jats:italic>C. albicans<\/jats:italic>\n              cell wall. Consequently, unmasked \u03b2(1,3)-glucan renders these cells more visible to the host immune system and attenuates disease progression. Therefore, discovery of how caspofungin-induced unmasking occurs is needed to elucidate how the drug facilitates host immune system-mediated clearance\n              <jats:italic>in vivo<\/jats:italic>\n              . We report a strong and consistent correlation between chitin deposition and unmasking in response to caspofungin and propose a model in which altered chitin synthesis drives increased unmasking during drug exposure.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.00074-23","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T13:00:57Z","timestamp":1687957257000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Caspofungin-induced \u03b2(1,3)-glucan exposure in\n            <i>Candida albicans<\/i>\n            is driven by increased chitin levels"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6777-4006","authenticated-orcid":true,"given":"Andrew S.","family":"Wagner","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Tennessee , Knoxville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen W.","family":"Lumsdaine","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Tennessee , Knoxville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikayla M.","family":"Mangrum","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Tennessee , Knoxville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2867-7182","authenticated-orcid":true,"given":"Todd B.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Tennessee , Knoxville, Tennessee, 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