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调查土耳其医院氟康唑耐药白念珠菌分离株 Erg11 基因的突变。

Investigation of mutations in Erg11 gene of fluconazole resistant Candida albicans isolates from Turkish hospitals.

机构信息

Department of Microbiology and Clinical Microbiology, School of Medicine, Dokuz Eylul University, Inciralti, Izmir, Turkey.

出版信息

Mycoses. 2011 Mar;54(2):99-104. doi: 10.1111/j.1439-0507.2009.01766.x.

Abstract

Widespread use of fluconazole has resulted in resistance in strains of Candida. The aim of our study was to investigate Y132H and other mutations in the ERG11 gene in conferring fluconazole resistance to C. albicans isolates. Seven fluconazole-resistant (R)/susceptible dose-dependent (SDD)/trailing and 10 fluconazole-susceptible (S) isolates were included. Restriction enzyme analysis was performed on all isolates for Y132H mutation and sequence analysis was performed for other mutations in the ERG11 gene. None of our strains had Y132H mutation. One single mutation (D153E, E266D, D116E, V437I) was detected in isolates 348, 533, 644, 1453, 2157, while the others had more than one nucleotide change. D116E and E266D, which were two mutations found in fluconazole R/SDD/trailing isolates with the highest frequency, were also detected in azole S strains. K143R, G464S, G465S and V488I mutations were determined in three of the R/SDD isolates. S412T and R469K mutations were detected only in this group of strains by sequence analysis. Mutations such as K143R, G464S, G465S, V488I, S412T and R469K in the ERG11 gene were determined to be effective mechanisms in our fluconazole R/SDD C. albicans isolates. Other mechanisms of resistance, such as overexpression of ERG11 and efflux pumps and mutations in the ERG3 gene should also be investigated.

摘要

氟康唑的广泛使用导致了念珠菌属菌株的耐药性。我们的研究目的是研究 ERG11 基因中的 Y132H 及其他突变在赋予白念珠菌分离株对氟康唑耐药性方面的作用。纳入了 7 株氟康唑耐药(R)/敏感剂量依赖性(SDD)/拖尾和 10 株氟康唑敏感(S)分离株。对所有分离株进行 Y132H 突变的限制性内切酶分析,并对 ERG11 基因中的其他突变进行序列分析。我们的菌株均无 Y132H 突变。在分离株 348、533、644、1453、2157 中检测到单个突变(D153E、E266D、D116E、V437I),而其他分离株则有多个核苷酸改变。D116E 和 E266D 是在氟康唑 R/SDD/拖尾分离株中发现的频率最高的两个突变,也在唑类 S 株中检测到。在 3 株 R/SDD 分离株中确定了 K143R、G464S、G465S 和 V488I 突变。通过序列分析仅在这组菌株中检测到 S412T 和 R469K 突变。在我们的氟康唑 R/SDD 白念珠菌分离株中,确定 ERG11 基因中的突变如 K143R、G464S、G465S、V488I、S412T 和 R469K 是有效的耐药机制。还应研究其他耐药机制,如 ERG11 和外排泵的过度表达以及 ERG3 基因的突变。

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