ERG11 mutations associated with azole resistance in Candida albicans isolates from vulvovaginal candidosis patients

• Published in: Asian Pacific journal of tropical biomedicine Vol. 5; no. 11; pp. 909 - 914
• Main Authors: Wang, Bin, Huang, Li-Hua, Zhao, Ji-Xue, Wei, Man, Fang, Hua, Wang, Dan-Yang, Wang, Hong-Fa, Yin, Ji-Gang, Xiang, Mei
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.11.2015; Wolters Kluwer Medknow Publications
• Subjects: albicans; Azoles; Azoles resistance; Candida; Candida albicans; ERG11; ERG11 gene; gene; Muta; Mutation; resistance; Vulvovaginal candidosis; Candida albicans; Azoles resistance; Vulvovaginal candidosis; Mutation; ERG11 gene
• ISSN: 2221-1691; 2588-9222
• DOI: 10.1016/j.apjtb.2015.08.002

Objective: To investigate the azole susceptibility of Candida albicans(C.albicans)from vulvovaginal candidosis patients and to analyze the relationship between ERG11 gene mutations in these isolates and azole resistance.Methods: Three hundred and two clinical isolates of Candida species were collected.Azole susceptibility was tested in vitro in microdilution studies. The ERG11 genes of 17 isolates of C. albicans(2 susceptibles, 5 dose-dependent resistants and 10 resistants) were amplified and sequenced.Results: Of the 302 isolates collected, 70.2% were C. albicans, of which 8.5%, 3.8% and4.2% were resistant to fluconazole, itraconazole and voriconazole, respectively. In total,27 missense mutations were detected in ERG11 genes from resistant/susceptible dosedependent isolates. Among them, Y132 H, A114 S, and Y257 H substitutions were most prevalent and were known to cause fluconazole resistance. G464 S and F72 S also have been proved to cause fluconazole resistance. Two novel substitutions(T285A, S457P) in hotspot regions were identified.Conclusions: Twenty seven mutations in the ERG11 gene were identified in azoleresistant C. albicans isolates, which indicated a possible relation with the increase in resistance to azole drugs and the recurrence of vulvovaginal candidosis. The relationship of two novel substitutions(T285A, S457P) with fluconazole resistance needs to be further verified by site-directed mutagenesis.