Extensive ERG11 mutations associated with fluconazole-resistant Candida albicans isolated from HIV-infected patients

Abstract

Background and Purpose: Azoles are preferred antifungal agents given their inexpensiveness, limited toxicity, and potentiality of oral administration. However, the extensive use of prophylactic azole therapy for chronic infections, especially in immunocompromised patients, has led to an increase in azole resistance, thereby rising health care costs. Fluconazole resistance is associated with poor clinical outcomes and the emergence of new infections. The present study aimed to investigate the mutations of ERG11 gene in fluconazole-resistant Candida albicans isolates. Materials and Methods: This study was conducted on 80 clinical samples collected from HIV-infected patients with suspected candidiasis in Tagore Medical College Hospital and Government Hospital of Thoracic Medicine, Chennai, India, for a period of 18 months (May 2016-December 2017). The antifungal susceptibility pattern was determined by agar diffusion and broth dilution techniques as per the Clinical and Laboratory Standards Institute guidelines. The ERG11 gene of the known fluconazole-resistant strains of C. albicans was amplified by polymerase chain reaction (PCR). In addition, the samples were subjected to sequencing and mutation analysis. Results: A total of 60 Candida species were isolated from HIV patients and were speciated using standard, conventional, and molecular methods. Candida albicans comprised 28.3% (n=17) of the Candida isolates, 59% (n=10) of which were resistant to fluconazole. Sequencing of the amplified product of ERG11 C. albicans gene isolates showed that they were highly mutated and included many nonsense mutations which were not reported earlier. Conclusion: The molecular characterization of ERG11 gene showed many missense and nonsense mutations. Such mutations, which were unique to the geographical area under investigation, could be concluded to account for the development of resistance to fluconazole.

Keywords

• aids
• antifungal resistance
• candida species
• candidiasis
• erg11
• fluconazole
• mutation