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Abstract

is a pathogenic yeast in humans, recognized for its genomic plasticity and increasing prevalence of antifungal resistance, including multidrug-resistant phenotypes, especially in the US and European countries.

This study hypothesizes that the resistance mechanisms in clinically resistant strains of differ from laboratory-generated resistant strains.

This study aims to understand the resistance mechanism in Indian clinical isolates of

A total of 240 clinical isolates of were tested for antifungal susceptibility and one resistant strain was artificially synthesized in the laboratory. Both clinical and lab-generated resistant strains were analysed for antifungal resistance using methods such as phenotypic assays, real-time quantitative PCR, Fluorescence-activated cell sorting (FACS) analysis and targeted gene sequencing. Mechanisms involving drug efflux pumps, mismatch repair pathways, ergosterol biosynthesis pathway and biofilm formation were systematically studied.

Among clinical isolates, one susceptible-dose dependent strain and three fluconazole-resistant strains were identified. Both clinical and lab-generated resistant strains demonstrated antifungal resistance phenotypically, with increased expression of . Targeted gene sequencing revealed novel mutations in , while mutations in served as genotypic markers for resistance. Overexpression of was seen in a lab-generated resistant strain where a specific mutation was identified. Biofilm activity contributed to resistance in one of the clinical strains.

This study reports for the first time the fluconazole resistance mechanism in from India. The findings underscore the diversity of resistance mechanisms among clinical and lab-generated isolates, emphasizing the need for novel antifungal therapies to address these emerging resistance profiles effectively.

Funding
This study was supported by the:
  • Department of Health and Research, Ministry of Health and Family Welfare, India (Award File No 12013/36/2020-HR)
    • Principal Award Recipient: pawarKalpana
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2025-11-25
2025-12-09

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