Molecular analysis of ERG11 gene in azole resistant Candida Species among immunocompromised patients

Abstract Background: Candida species are opportunistic pathogens that can cause life-threatening infections, especially in immunocompromised patients. Azole antifungals are widely used for treatment, but resistance is increasing and often due to mutations in the ERG11gene that compromises their efficacy. Objectives: To determine the prevalence of azole-resistant Candida spp. among immunocompromised patients and identify mutations in the ERG11 gene associated with resistance. Methods: In this cross-sectional study, clinical samples were processed from immunocompromised patients at two University Hospitals in Egypt. Identification of Candida spp. was done using culture, chromogenic media, and VITEK 2 system. Susceptibility to fluconazole and voriconazole was assessed using broth microdilution method. Resistant isolates were subjected to PCR amplification and Sanger sequencing of ERG11 hot spot regions. Results: Out of 1404 eligible samples, 90 (6.4%) yielded Candida spp., predominantly C. tropicalis(44.4%) and C. albicans (41.1%). Resistance to fluconazole and voriconazole was observed in 14.4% and 13.3% of isolates, respectively. ERG11sequencing revealed multiple mutations. Common missense mutations included Y132F (50%) and S154F (33.3%). A novel mutation (M306R) was identified in two C. tropicalis isolates. Conclusion: Azole resistance among Candidaisolates is notable in immunocompromised patients. The present study highlights both known and novel ERG11 mutations, emphasizing the need for routine molecular surveillance to guide antifungal therapy.