{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:53:53Z","timestamp":1791986033998,"version":"4.4.0"},"reference-count":82,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"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":["mBio"],"published-print":{"date-parts":[[2026,4,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Candida tropicalis<\/jats:italic>\n                      is a leading cause of invasive candidiasis in the Asia-Pacific region with reported crude mortality rates exceeding 50%. The rising prevalence of azole-resistant strains presents a significant clinical challenge. We analyzed 1,016\n                      <jats:italic toggle=\"yes\">C. tropicalis<\/jats:italic>\n                      clinical isolates collected over nine years from 27 hospitals across North India. Fluconazole resistance was detected in 5.1% (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 52) of isolates, with cross-resistance observed to voriconazole in 55.7% and itraconazole in 44.2% of isolates. Multilocus sequence typing (MLST) analysis of global 1,630 isolates including 208 Indian and whole-genome sequencing of 716 global isolates (139 Indian) confirmed the clonal emergence and persistence of azole-resistant MLST clade 4 strains in Indian hospitals. Phylogenomic analyses identified that Indian azole-resistant lineage was closely related to azole-resistant isolates from mainland China and Taiwan. The underlying mechanism of resistance involved hotspot mutations (Y132F) in the\n                      <jats:italic toggle=\"yes\">ERG11<\/jats:italic>\n                      gene along with its duplication, overexpression, and twofold high ergosterol content. Comparative transcriptomics of two clinical isolates exhibiting &gt;512 fold difference in fluconazole susceptibility identified upregulation of virulence-associated genes,\n                      <jats:italic toggle=\"yes\">ALS7<\/jats:italic>\n                      gene (eightfold),\n                      <jats:italic toggle=\"yes\">SAP7<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">SAP9<\/jats:italic>\n                      (1.6- and 2-fold, respectively) in azole-resistant isolate. Furthermore, azole-resistant isolates showed robust biofilm-associated metabolic activity (twofold), reduced \u03b2-glucan exposure, and greater survival in both neutrophil and macrophage killing assays. Notably, azole-resistant lineage exhibits several traits associated with adhesion and immune evasion that could possibly enable its spread in healthcare settings and signals the beginning of a greater spread of this clone. The urgent need for continuous genomic surveillance and antifungal stewardship is warranted to mitigate the spread of multidrug-resistant\n                      <jats:italic toggle=\"yes\">C. tropicalis<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Invasive fungal infections affect 6.5 million people annually and are associated with high mortality rates. Despite being the leading cause of invasive yeast infections in the Asia-Pacific, this is the first comprehensive study of\n                        <jats:italic toggle=\"yes\">Candida tropicalis<\/jats:italic>\n                        from India documenting the emergence of azole-resistant clonal lineage (clade 4) in several hospitals in India. Azole resistance is driven by mutations, gene duplication, and overexpression of its target gene\n                        <jats:italic toggle=\"yes\">ERG11<\/jats:italic>\n                        . The Indian azole-resistant isolates showed high genetic relatedness with those from China. Also, resistant isolate showed overexpression of virulence-related genes and robust biofilm formation. Notably, reduced \u03b2-glucan exposure in fluconazole-resistant isolates may contribute to their decreased susceptibility to the innate immune system. Importantly, this study provides evidence for the emergence of azole-resistant\n                        <jats:italic toggle=\"yes\">C. tropicalis<\/jats:italic>\n                        lineage in India, which exhibits several traits associated with adhesion and immune evasion that could possibly enable its spread in healthcare settings leading to a public health concern.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.00235-26","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T13:02:23Z","timestamp":1773234143000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Genomic insights into a clade-specific\n                    <i>Candida tropicalis<\/i>\n                    lineage with resistance to azoles and immune evasion 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