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

• Autor(a) principal: Benedetti,Volmir Pitt
• Data de Publicação: 2019
• Outros Autores: Savi,Daiani Cristina, Aluizio,Rodrigo, Adamoski,Douglas, Kava,Vanessa, Galli-Terasawa,Lygia Vitória, Glienke,Chirlei
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Revista da Sociedade Brasileira de Medicina Tropical
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822019000100311
• topic: Candida albicans; Drug Resistance; Fluconazole; Sterol; 14α-demethylase

Abstract INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.