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An increase of breakthrough infections has been found in cohorts receiving short-tailed azoles prophylaxis (e.g. voriconazole (VCZ)). Although VCZ is ineffective\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    , long-tailed triazoles such as posaconazole remain active against mucormycetes. Our goal was to validate the molecular mechanism of resistance to short-tailed triazoles in Mucorales. The paralogous cytochrome P450 genes (CYP51 F1 and CYP51 F5) of\n                    <jats:italic>Rhizopus arrhizus<\/jats:italic>\n                    ,\n                    <jats:italic>Rhizopus microsporus<\/jats:italic>\n                    , and\n                    <jats:italic>Mucor circinelloides<\/jats:italic>\n                    were amplified and sequenced. Alignment of the protein sequences of the\n                    <jats:italic>R. arrhizus<\/jats:italic>\n                    ,\n                    <jats:italic>R. microsporus<\/jats:italic>\n                    , and\n                    <jats:italic>M. circinelloides<\/jats:italic>\n                    CYP51 F1 and F5 with additional Mucorales species (n\u2009=\u20093) and other fungi (n\u2009=\u200916) confirmed the sequences to be lanosterol 14\u03b1-demethylases (LDMs). Sequence alignment identified a pan-Mucorales conservation of a phenylalanine129 substitution in all CYP51 F5s analyzed. A high resolution X-ray crystal structure of\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    LDM in complex with VCZ was used for generating a homology model of\n                    <jats:italic>R. arrhizus<\/jats:italic>\n                    CYP51 F5. Structural and functional knowledge of\n                    <jats:italic>S. cerevisiae<\/jats:italic>\n                    CYP51 shows that the F129 residue in Mucorales CYP51 F5 is responsible for intrinsic resistance of Mucorales against short-tailed triazoles, with a V to A substitution in Helix I also potentially playing a role.\n                  <\/jats:p>","DOI":"10.1038\/s41598-017-16123-9","type":"journal-article","created":{"date-parts":[[2017,11,15]],"date-time":"2017-11-15T06:05:05Z","timestamp":1510725905000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["Intrinsic short-tailed azole resistance in mucormycetes is due to an evolutionary conserved aminoacid substitution of the lanosterol 14\u03b1-demethylase"],"prefix":"10.1038","volume":"7","author":[{"given":"Rita","family":"Caramalho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel D. 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