Related Experiment Video
Updated: May 12, 2026
Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
Hsp21 potentiates antifungal drug tolerance in Candida albicans
François L Mayer1, Duncan Wilson, Bernhard Hube
1Department of Microbial Pathogenicity Mechanisms, Hans-Knoell-Institute, Jena, Germany.
Abstract:
Systemic infections of humans with the fungal pathogen Candida albicans are associated with a high mortality rate. Currently, efficient treatment of these infections is hampered by the relatively low number of available antifungal drugs. We recently identified the small heat shock protein Hsp21 in C. albicans and demonstrated its fundamental role for environmental stress adaptation and fungal virulence. Hsp21 was found in several pathogenic Candida species but not in humans. This prompted us to investigate the effects of a broad range of different antifungal drugs on an Hsp21-null C. albicans mutant strain. Our results indicate that combinatorial therapy targeting Hsp21, together with specific antifungal drug targets, has strong synergistic potential. In addition, we demonstrate that Hsp21 is required for tolerance to ethanol-induced stress and induction of filamentation in response to pharmacological inhibition of Hsp90. These findings might pave the way for the development of new treatment strategies against Candida infections.
Insights
Targeting the fungal protein Hsp21 in Candida albicans, alongside existing antifungal drugs, shows promise for treating systemic infections. This approach may overcome current treatment limitations and improve patient outcomes.
Area of Science:
- Mycology
- Infectious Diseases
- Biochemistry
Background:
- Systemic Candida albicans infections have high mortality rates.
- Limited antifungal drug options hinder effective treatment.
- The small heat shock protein Hsp21 is crucial for Candida stress adaptation and virulence and is absent in humans.
Purpose of the Study:
- To investigate the therapeutic potential of targeting Hsp21 in Candida albicans.
- To evaluate the synergistic effects of combining Hsp21 inhibition with existing antifungal drugs.
- To explore Hsp21's role in stress tolerance and filamentation.
Main Methods:
- Generation of an Hsp21-null Candida albicans mutant strain.
- Screening of various antifungal drugs against the mutant.
- Assessment of Hsp21's role in ethanol stress tolerance and filamentation upon Hsp90 inhibition.
Main Results:
- Combinatorial therapy targeting Hsp21 demonstrated significant synergistic potential with specific antifungal drugs.
- Hsp21 was found to be essential for tolerance to ethanol-induced stress.
- Hsp21 plays a role in the induction of filamentation when Hsp90 is pharmacologically inhibited.
Conclusions:
- Targeting Hsp21 offers a promising strategy for novel combination therapies against Candida infections.
- Hsp21 is a key factor in Candida's response to environmental stressors and drug treatments.
- These findings may lead to the development of more effective treatments for invasive fungal diseases.
