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Relationship between antifungal resistance of fluconazole resistant Candida albicans and mutations in ERG11 gene

摘要Background The cytochrome P450 lanosterol 14α-demethylase(Erg11p) encoded by ERG11 gene is the primary target for azole antifungals.Changes in azole affinity of this enzyme caused by amino acid substitutions have been reported as a mechanism of azole antifungal resistance. This study aimed to investigate the relationship between amino acid substitutions in Erg11p from fluconazole resistant Candida albicans (C.albicans)isolates and their cross-resistance to azoles.Methods Mutations in ERG11 gene were screened in 10 clinical isolates of fluconazole resistant C.albicans strains.DNA sequence of ERG11 was determined by PCR based DNA sequencing.Results In the 10 isolates,19 types of amino acid substitutions were found,of which 10 substitutions (F72S, F103L, F145I, F198L, G206D, G227D, N349S, F416S, F422L and T482A) have not been reported previously. Mutations in ERG11 gene were detected in 9 isolates of fluconazole resistant C. albicans, but were not detected in 1 isolate. Conclusions Although no definite correlation was found between the type of amino acid substitutions in Erg11p and the phenotype of cross-resistance to azoles, the substitutions F72S, F145I and G227D in our study may be highly associated with resistance to azoles because of their special location in Erg11p.

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作者单位 Research Center for Medical Mycology,Peking University,Beijing 100034,China [1]
分类号 R3
栏目名称 ORIGINAL ARTICLES
DOI 10.3760/cma.j.issn.0366-6999.2010.05.007
发布时间 2010-05-10
基金项目
This work was supported by a grant from the Key Project of Chinese Ministry of Education
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中华医学杂志(英文版)

中华医学杂志(英文版)

2010年123卷5期

544-548页

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