{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:23:46Z","timestamp":1788269026549,"version":"build-2803163510"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Candida glabrata<\/jats:italic>\n                      is an opportunistic yeast that causes invasive infections in immunocompromised individuals. Echinocandin antifungals are first-line agents in the treatment of invasive candidiasis and act by inhibiting fungal cell wall synthesis by targeting \u03b2-1,3-glucan synthase. Echinocandin resistance is primarily associated with mutations in\n                      <jats:italic toggle=\"yes\">FKS1<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">FKS2<\/jats:italic>\n                      , which encode for the catalytic subunit (Fks1 or Fks2) of the targeted glucan synthase. The cell wall integrity (CWI) pathway, including Slt2 kinase, is known to mediate tolerance to antifungal drugs, but its role in resistance is not completely defined. Here, we observed that disruption of\n                      <jats:italic toggle=\"yes\">SLT2<\/jats:italic>\n                      abrogated echinocandin resistance due to\n                      <jats:italic toggle=\"yes\">FKS2<\/jats:italic>\n                      , but not\n                      <jats:italic toggle=\"yes\">FKS1,<\/jats:italic>\n                      mutation in\n                      <jats:italic toggle=\"yes\">C. glabrata<\/jats:italic>\n                      . As expected, reintroduction of plasmid-borne\n                      <jats:italic toggle=\"yes\">SLT2<\/jats:italic>\n                      restored elevated MICs of\n                      <jats:italic toggle=\"yes\">fks2<\/jats:italic>\n                      mutants. RT-qPCR revealed that loss of\n                      <jats:italic toggle=\"yes\">SLT2<\/jats:italic>\n                      led to decreased\n                      <jats:italic toggle=\"yes\">FKS2<\/jats:italic>\n                      expression levels in wild-type and echinocandin-resistant strains following echinocandin exposure. In conclusion, the CWI pathway and Slt2 comprise a primary control mechanism for\n                      <jats:italic toggle=\"yes\">FKS2<\/jats:italic>\n                      -mediated echinocandin resistance in\n                      <jats:italic toggle=\"yes\">C. glabrata<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The higher rates of acquired antifungal resistance exhibited by\n                        <jats:italic toggle=\"yes\">Candida glabrata<\/jats:italic>\n                        merit further understanding of resistance mechanisms including fungal regulation of drug target genes and enzymes. Here, we focused on a fungal tolerance pathway, the cell wall integrity pathway, and its requirement in\n                        <jats:italic toggle=\"yes\">C. glabrata<\/jats:italic>\n                        echinocandin antifungal resistance. Interestingly, we found that targeting the pathway through disruption of a key protein, Slt2, reversed echinocandin resistance within one subset of resistant strains (\n                        <jats:italic toggle=\"yes\">fks2<\/jats:italic>\n                        mutants) but not another (\n                        <jats:italic toggle=\"yes\">fks1<\/jats:italic>\n                        mutants). Gene expression studies demonstrated the requirement of\n                        <jats:italic toggle=\"yes\">SLT2<\/jats:italic>\n                        for full\n                        <jats:italic toggle=\"yes\">FKS2<\/jats:italic>\n                        gene expression following echinocandin treatment. Overall, we discovered that Slt2 is specifically required for Fks2-mediated echinocandin resistance through partial regulation of\n                        <jats:italic toggle=\"yes\">FKS2<\/jats:italic>\n                        expression. This study provides further insight into the regulation of drug target genes in\n                        <jats:italic toggle=\"yes\">C. glabrata<\/jats:italic>\n                        and provides a possible therapeutic target for echinocandin-resistant infections caused by mutation of\n                        <jats:italic toggle=\"yes\">FKS2<\/jats:italic>\n                        .\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03874-25","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:00:06Z","timestamp":1786366806000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Slt2 kinase of the cell wall integrity pathway is required for Fks2-specific echinocandin resistance in\n                    <i>Candida glabrata<\/i>"],"prefix":"10.1128","volume":"14","author":[{"given":"Zubayeda","family":"Uddin","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00k3ayt93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, William Paterson University","place":["Wayne, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saira","family":"Tahsin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00k3ayt93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, William Paterson University","place":["Wayne, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Valickova","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00k3ayt93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, William Paterson University","place":["Wayne, 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Performance standards for antifungal susceptibility testing of yeasts. In CLSI supplement M60. 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