ERG11 gene polymorphisms and susceptibility to fluconazole in Candida isolates from diabetic and kidney transplant patients

• Published in: Revista da Sociedade Brasileira de Medicina Tropical 2019-01, Vol.52, p.e20180473-e20180473
• Main Authors: Benedetti, Volmir Pitt, Savi, Daiani Cristina, Aluizio, Rodrigo, Adamoski, Douglas, Kava, Vanessa, Galli-Terasawa, Lygia Vitória, Glienke, Chirlei
• Format: Article
• Language: English
• Subjects: 14α-demethylase; Adult; Aged; Antifungal Agents - pharmacology; Candida - drug effects; Candida - genetics; Candida - isolation & purification; Candida albicans; Diabetes Mellitus - microbiology; DNA, Fungal - genetics; Drug Resistance; Drug Resistance, Fungal - genetics; Female; Fluconazole; Fluconazole - pharmacology; Humans; Immunocompetence; Kidney Transplantation; Male; Microbial Sensitivity Tests; Middle Aged; Mutation - drug effects; Polymerase Chain Reaction; Polymorphism, Genetic - drug effects; Reference Values; Saliva - microbiology; Sterol; TROPICAL MEDICINE
• ISSN: 0037-8682; 1678-9849; 1678-9849
• DOI: 10.1590/0037-8682-0473-2018

Candidiasis is the most frequent opportunistic mycosis in humans and can cause mortality, particularly in immunodeficient patients. One major concern is the increasing number of infections caused by drug-resistant Candidas trains, as these cannot be efficiently treated with standard therapeutics. The most common mechanism of fluconazole resistance in Candida is mutation of ERG11, a gene involved in the biosynthesis of ergosterol, a compound essential for cell integrity and membrane function. Based on this knowledge, we investigated polymorphisms in the ERG11 gene of 3 Candida species isolated from immunocompromised and immunocompetent patients. In addition, we correlated the genetic data with the fluconazole susceptibility profile of the Candida isolates. A total of 80 Candida albicans, 8 Candida tropicalis and 6 Candida glabrata isolates were obtained from the saliva of diabetic, kidney transplant and immunocompetent patients. Isolates were considered susceptible to fluconazole if the minimum inhibitory concentration was lower than 8 μg/mL. The amino acid mutations F105L, D116E, K119N, S137L, and K128T were observed in C. albicans isolates, and T224C and G263A were found in C. tropicalis isolates. Despite the high number of polymorphisms observed, the mutations occurred in regions that are not predicted to interfere with ergosterol synthesis, and therefore are not related to fluconazole resistance.