Molecular Confirmation of the Linkage between the Rhizopus oryzae CYP51A Gene Coding Region and Its Intrinsic Voriconazole and Fluconazole Resistance.

Antimicrobial agents and chemotherapy(2018)

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摘要
is the most prevalent causative agent of Mucormycosis, an increasingly reported opportunistic fungal infection. These mucormycetes are intrinsically resistant to - and -active antifungal azole drugs such as fluconazole and voriconazole, respectively. Despite of its importance, the molecular mechanisms of its intrinsic azole resistance have not been elucidated yet. The aim of this work is to establish if the genes are the unique responsible for voriconazole and fluconazole intrinsic resistance in these fungal pathogens. Two genes were identified in genome. We classify them as and based on their sequence similarity with other known fungal genes. Later, we obtained a chimerical strain harboring a functional gene expressed under the regulation of wild type promoter and terminator. The mutant was selected after transformation by using a novel procedure taking advantage of the FLC-hypersusceptibility of the used deletant mutant as recipient strain. The transformants harboring the mimicked exactly the azole susceptibility patterns of this Mucormycete. The data presented in this work demonstrate that coding sequence is the unique responsible of the azole susceptibility patterns.
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关键词
azole,CYP51,intrinsic resistance,molecular mechanism,resistance,Rhizopus,fluconazole,Mucorales,voriconazole
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