Oliveira Carvalho Vagner, Okay Thelma S, Melhem Márcia S C, Walderez Szeszs Maria, del Negro Gilda M B
Laboratory of Medical Mycology (LIM-53)-Clinical Dermatology Division, Hospital das Clínicas da FMUSP e Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, São Paulo, State of São Paulo, Brazil.
Rev Iberoam Micol. 2013 Jul-Sep;30(3):209-12. doi: 10.1016/j.riam.2013.01.001. Epub 2013 Feb 9.
For many years fluconazole has been commonly used to treat Candida infections. However, the indiscriminate use of this antimycotic therapy has favored the emergence of resistant isolates. Mutations in the ERG11 gene have been described as one of the primary mechanisms of resistance in Candida species.
In this study we investigated missense mutations in ERG11 genes of Candida albicans, Candida glabrata and Candida tropicalis isolates previously evaluated by susceptibility testing to fluconazole.
Screening for these mutations was performed on 19 Candida clinical isolates (eight C. albicans, five C. glabrata and six C. tropicalis) resistant and susceptible to fluconazole. The ERG11 gene was amplified by PCR with specific primers for each Candida species and analyzed by automated sequencing.
We identified 14 different missense mutations, five of which had not been described previously. Among them, a new mutation L321F was identified in a fluconazole resistant C. albicans isolate and it was analyzed by a theoretical three-dimensional structure of the ERG11p.
The L321F mutation in C. albicans ERG11 gene may be associated with fluconazole resistance.
多年来，氟康唑一直被广泛用于治疗念珠菌感染。然而，这种抗真菌疗法的滥用促使了耐药菌株的出现。ERG11基因突变已被描述为念珠菌属耐药的主要机制之一。
在本研究中，我们调查了白色念珠菌、光滑念珠菌和热带念珠菌分离株ERG11基因中的错义突变，这些分离株之前已通过氟康唑敏感性试验进行评估。
对19株对氟康唑耐药和敏感的念珠菌临床分离株（8株白色念珠菌、5株光滑念珠菌和6株热带念珠菌）进行这些突变的筛查。使用针对每种念珠菌的特异性引物通过PCR扩增ERG11基因，并通过自动测序进行分析。
我们鉴定出14种不同的错义突变，其中5种此前未被描述过。其中，在一株对氟康唑耐药的白色念珠菌分离株中鉴定出一种新的突变L321F，并通过ERG11p的理论三维结构对其进行了分析。
白色念珠菌ERG11基因中的L321F突变可能与氟康唑耐药有关。
