ERG11 gene polymorphisms and susceptibility to fluconazole in candida isolates from diabetic and kidney transplant patients
Rev. Soc. Bras. Med. Trop; 52 (), 2019
Publication year: 2019
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.
Antifúngicos/farmacología, Candida/efectos de los fármacos, Candida/genética, Candida/aislamiento & purificación, ADN de Hongos/genética, Diabetes Mellitus/microbiología, Farmacorresistencia Fúngica/genética, Fluconazol/farmacología, Inmunocompetencia, Trasplante de Riñón, Pruebas de Sensibilidad Microbiana, Persona de Mediana Edad, Mutación/efectos de los fármacos, Reacción en Cadena de la Polimerasa, Polimorfismo Genético/efectos de los fármacos, Valores de Referencia, Saliva/microbiología