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

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 ERG11 gene that compromises their efficacy. This study aimed to determine the prevalence of azole-resistant Candida spp. among immunocompromised patients and identify mutations in the ERG11 gene associated with resistance.

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 on Sabouraud's Dextrose agar as well as Candida Differential agar supplemented by automated identification by the mass spectrometry method (MALDI-TOF, Vitek MS, bioMérieux, France). 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.

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. ERG11 sequencing revealed multiple mutations. Common missense mutations included Y132F (50%) and S154F (33.3%). A novel mutation (M306R) was identified in two C. tropicalis isolates.

Azole resistance among Candida isolates 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.