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Updated: Jan 1, 2026
Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
Extensive ERG11 mutations associated with fluconazole-resistant Candida albicans isolated from HIV-infected patients
Sony Paul1, Iyanar Kannan1, Kalyani Mohanram2
1Department of Microbiology, Tagore Medical College and Hospital, Rathinamangalam, Chennai, India.
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.
Insights
Fluconazole resistance in Candida albicans is increasing due to ERG11 gene mutations. This study identified unique mutations in HIV patients, highlighting a need for new antifungal strategies.
Area of Science:
- Mycology
- Medical Microbiology
- Molecular Biology
Background:
- Azoles are common antifungals but widespread use has led to resistance.
- Fluconazole resistance in Candida albicans is a growing concern, especially in immunocompromised patients.
- Resistance is linked to poor patient outcomes and increased healthcare costs.
Purpose of the Study:
- To investigate mutations in the ERG11 gene of fluconazole-resistant Candida albicans isolates.
- To understand the genetic basis of antifungal resistance in a specific patient population.
Main Methods:
- Collected clinical samples from HIV-infected patients with suspected candidiasis.
- Determined antifungal susceptibility using standard microbiological techniques.
- Amplified and sequenced the ERG11 gene from resistant Candida albicans strains using PCR.
Main Results:
- Identified Candida albicans in 17 out of 60 Candida isolates (28.3%).
- Found that 59% (10 isolates) of Candida albicans were resistant to fluconazole.
- Discovered numerous novel missense and nonsense mutations in the ERG11 gene of resistant strains.
Conclusions:
- The ERG11 gene in fluconazole-resistant Candida albicans exhibits significant mutations.
- These unique mutations may be responsible for the observed fluconazole resistance in the studied population.
- Findings suggest potential for targeted antifungal therapies based on specific genetic markers.
