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Azole potentiation in Candida species
Jan S Stenkiewicz-Witeska1, Iuliana V Ene1
1Institut Pasteur, Université Paris Cité, Fungal Heterogeneity Group, Paris, France.
Abstract:
Fungal infections are rising, with over 1.5 billion cases and more than 1 million deaths recorded each year. Among these, Candida infections are frequent in at-risk populations and the rapid development of drug resistance and tolerance contributes to their clinical persistence. Few antifungal drugs are available, and their efficacy is declining due to the environmental overuse and the expansion of multidrug-resistant species. One way to prolong their utility is by applying them in combination therapy. Here, we highlight recently described azole potentiators belonging to different categories: natural, repurposed, or novel compounds. We showcase examples of molecules and discuss their identified or proposed mode of action. We also emphasise the challenges in azole potentiator development, compounded by the lack of animal testing, the overreliance on Candida albicans and Candida auris, as well as the limited understanding of compound efficacy.
Insights
Rising fungal infections and drug resistance necessitate new strategies. This study reviews azole potentiators, including natural, repurposed, and novel compounds, to enhance antifungal drug efficacy and combat resistance.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Pharmacology
Background:
- Fungal infections cause over 1.5 billion cases and 1 million deaths annually.
- Candida infections are prevalent in vulnerable groups, with increasing drug resistance and tolerance.
- Limited antifungal drug options and widespread resistance due to overuse necessitate combination therapies.
Purpose of the Study:
- To review recently identified azole potentiators.
- To discuss the modes of action for these compounds.
- To highlight challenges in developing azole potentiators.
Main Methods:
- Literature review of azole potentiators.
- Categorization of potentiators into natural, repurposed, and novel compounds.
- Analysis of proposed mechanisms of action.
Main Results:
- Several categories of azole potentiators have been identified.
- Examples of specific molecules and their proposed actions are presented.
- Challenges include limited animal testing and overreliance on specific Candida species.
Conclusions:
- Azole potentiators offer a promising strategy to overcome antifungal drug resistance.
- Further research is needed to address development challenges and expand efficacy understanding.
- Combination therapy with azole potentiators could prolong the utility of existing antifungal drugs.
