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

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.

Pola Kepekaan Candida krusei Isolat Jakarta terhadap Flukonazol

“…Baik profil basa DNA di daerah ribosom yakni wilayah internal spacer dan large sub unit (ITS region dan LSU) maupun profil/ aktivitas gene ERG11 yang terlibat dalam proses biosintesis ergosterol melalui penyandian enzim yang terlibat dalam proses tersebut. [17][18][19][20] Saat ini penelitian tentang sifat genetik jamur ini tengah berlansung.…”

Detection of ERG11 gene in fluconazole resistant urinary candida isolates

“…Unfortunately, the widespread continuous use of fluconazole enhanced the resistance to the drug. 11 Voriconazole is a second-generation broadspectrum triazole antifungal agent with activity against a wide range of yeasts and filamentous fungi. It is used to treat severe invasive fungal infections.…”