Characterization of ERG11 Gene in Drug-Resistant Candida Albicans Isolated from Iranian Cases of Recurrent Vulvovaginal Candidiasis

 Candida albicans is the most common fungal pathogen of human infections. C. albicans is responsible for significant mucosal infections such as vulvovaginitis in women. Azoles inhibit the cytochrome P450 14α-lanosterol demethylase, as a part of the ergosterol biosynthetic pathway is encoded by the ERG11 gene. Some mutations in ERG 11 could cause resistance to azole drugs.  Detection of the mutations of the gene in the present study helped us to explain drug resistances in some vaginal isolates of C. albicans and other Candida species.

A multicenter, experimental study was conducted at Cellular and Molecular Research Center and Kowsar Gynecology Center affiliated to UMSU from October 2016 to July 2017. Women with symptomatic vaginitis (20-45 years old) were asked to take part in the study. 192 women allowed vaginal swabs to be obtained. For the identifications, culture on SGA4% and CHROM agar Candida were conducted followed by PCR-RFLP. A disc diffusion method was performed based on the standard guideline of the National Committee for Clinical Laboratory Standards (NCCLS) to determine level of susceptibility against fluconazole and clotrimazole (most current use for the treatment of VVC). DNA extraction and PCR amplification of the ERG11 gene were performed.

As we showed in the Table (1), 69.1% of all Candida isolates carried the ERG11 gene. It was detected in 49(68.1%), 5 (55.6%), and 7(77.8%) cases of C. albicans, C. krusei, and C. glabrata, respectively.  Among the C. albicans isolates resistant to Clotrimazole, 8(53.3%) had ERG11 gene while 7(46.7%) did not. Among all the C. glabrata isolates resistant to Clotrimazole, 40% carried ERG11 while 60% did not show the gene. Also, ERG11 gene was detected in 50% of the isolated C. glabrata. ERG11 gene was observed in 53.3% of C.krusei isolates resistant to Clotrimazole and 52% of those of resistant to Fluconazole.

As an approximate finding, Azole resistance in the present study could be attributed to mutations in ERG11 gene