Related Experiment Videos
[Azole resistance in Candida albicans]
1Department of Medicine, Division of Infectious Diseases, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., 7881 San Antonio, TX, USA.
Summary
Azole antifungal resistance in Candida albicans, particularly fluconazole resistance in HIV-infected patients with oropharyngeal candidiasis, is driven by target enzyme alterations and efflux pump overexpression. Multifactorial resistance mechanisms necessitate new therapeutic strategies.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
- Molecular Biology
Background:
- Azole antifungal resistance in Candida albicans involves target enzyme modifications and increased drug efflux.
- While systemic azole resistance is low, fluconazole resistance is a significant challenge in managing oropharyngeal candidiasis (OPC) in patients with acquired immunodeficiency syndrome (AIDS).
Purpose of the Study:
- To investigate the prevalence and molecular mechanisms of azole antifungal resistance in highly resistant Candida albicans isolates from HIV-infected patients with OPC.
- To analyze the genetic basis of resistance, including target enzyme alterations and efflux transporter gene expression.
Main Methods:
- Antifungal susceptibility testing using NCCLS methodology.
- DNA typing for strain identification.
- Monitoring overexpression of erg11, mdr1, and cdr genes.
- PCR amplification and sequencing of erg11 genes to detect point mutations.
Main Results:
- A combination of molecular mechanisms contributed to fluconazole resistance in the studied Candida albicans isolates.
- Overexpression of genes encoding lanosterol 14-demethylase (erg11) and efflux transporters (mdr1, cdr) was observed.
- Point mutations in erg11 genes were identified as a factor in resistance.
Conclusions:
- The multifactorial nature of azole resistance in Candida albicans necessitates the development of novel therapeutic approaches.
- Ongoing research includes developing new triazoles, investigating new antifungal classes, and exploring combinations with efflux transporter inhibitors.