Department of Dermatology, Peking University First Hospital; Research Center for Medical Mycology, Peking University, Beijing 100034, China.
Chin Med J (Engl). 2010 Mar 5;123(5):544-8.
The cytochrome P450 lanosterol 14alpha-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.
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.
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.
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.
细胞色素 P450 羊毛甾醇 14α-脱甲基酶（Erg11p）由 ERG11 基因编码，是唑类抗真菌药物的主要作用靶点。已有报道称，该酶的唑类亲和力的改变是唑类抗真菌药物耐药的机制之一，这种改变是由氨基酸取代引起的。本研究旨在探讨氟康唑耐药白念珠菌（Candida albicans）分离株 Erg11p 中的氨基酸取代与唑类交叉耐药之间的关系。
筛选 10 株氟康唑耐药白念珠菌临床分离株中 ERG11 基因的突变。通过基于 PCR 的 DNA 测序确定 ERG11 基因的 DNA 序列。
在这 10 株分离株中，发现了 19 种类型的氨基酸取代，其中 10 种取代（F72S、F103L、F145I、F198L、G206D、G227D、N349S、F416S、F422L 和 T482A）以前尚未报道过。在 9 株氟康唑耐药白念珠菌分离株中检测到 ERG11 基因突变，但在 1 株分离株中未检测到。
虽然 Erg11p 中的氨基酸取代类型与唑类交叉耐药表型之间未发现明确的相关性，但我们研究中 F72S、F145I 和 G227D 这 3 种取代可能与唑类耐药高度相关，因为它们位于 Erg11p 的特殊位置。
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