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Treatment options are limited. These include debridement of necrotizing tissue followed by complicated multicomponent therapies with amphotericin B and selected azole drugs, usually having poor outcomes. Mucormycetes are intrinsically resistant to the widely used short-tailed azole drugs fluconazole and voriconazole, but susceptible to the long-tailed, though expensive, azole posaconazole. Knowledge of the crystal structure of\n                      <jats:italic toggle=\"yes\">Saccharomyces cerevisiae<\/jats:italic>\n                      sterol 14\u03b1-demethylase (Erg11, Cyp51) led to the hypothesis that this pattern of intrinsic azole resistance and susceptibility is due to the\n                      <jats:italic toggle=\"yes\">Rhizopus arrhizus<\/jats:italic>\n                      CYP51-F5 isoform residues F129 and A291, while the CYP51-F1 isoform residues Y127 and V291 confer susceptibility to both short- and long-tailed azole drugs. 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Complementary gene deletion experiments in\n                      <jats:italic toggle=\"yes\">Rhizopus microsporus<\/jats:italic>\n                      confirm that the amino acid residues that align with\n                      <jats:italic toggle=\"yes\">R. arrhizus<\/jats:italic>\n                      CYP51-F5 F129 and A291 determine the resistance or susceptibility pattern of\n                      <jats:italic toggle=\"yes\">R. arrhizus<\/jats:italic>\n                      to short-, medium-, and long-tailed azoles.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01337-25","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T11:03:44Z","timestamp":1764932624000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["The molecular basis of intrinsic resistance to azoles in\n                    <i>Rhizopus 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