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Updated: Aug 13, 2026
Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
An investigation into uptake and delivery of oligonucleotides in Candida
Antwine W McFarland1, Sandra P Story1, Dev P Arya2
1NUBAD LLC, Greer, SC 29650, USA.
Abstract:
Candida represent a leading cause of morbidity and mortality worldwide resulting from opportunistic fungal infections. Increasing antifungal resistance calls for new ways of treating multidrug resistant fungal infections. Antisense oligonucleotides that target essential genes can offer a new treatment option; however, uptake of oligonucleotides presents the problem of passage across cell membrane and/or cell wall layers. Liposomes have been used to deliver pharmaceutical drugs, proteins, and nucleic acids to a variety of bacterial and eukaryotic cells. Here we investigated the utilization of commercially available liposomes to facilitate uptake of antisense oligonucleotides in Candida. Dynamic light scattering analysis determined the method which produced the most uniform commercially available liposome. Flow cytometry revealed which liposome composition facilitated the best delivery of fluorescein-labeled oligonucleotides in planktonic cells of Candida albicans, Candida auris and Candida glabrata. A time dependent uptake of liposomes within Candida biofilms demonstrated delivery of fluorescein-tagged DNA in Candida glabrata by 24 h. Efficient delivery of antisense-EFG1 was further indicated by a corresponding reduction in C. albicans hyphae length and number as well as a reduction in the levels of EFG1 gene expression.
Insights
Liposomes effectively deliver antisense oligonucleotides into Candida species, addressing antifungal resistance. This novel approach enhances drug delivery for treating multidrug-resistant fungal infections.
Area of Science:
- Mycology
- Antimicrobial Resistance
- Drug Delivery Systems
Background:
- Candida species are significant causes of opportunistic fungal infections, leading to substantial global morbidity and mortality.
- Rising antifungal resistance necessitates innovative therapeutic strategies for multidrug-resistant fungal infections.
- Antisense oligonucleotides offer a potential treatment avenue, but cellular uptake remains a challenge.
Purpose of the Study:
- To investigate the use of commercially available liposomes for enhancing antisense oligonucleotide uptake in Candida species.
- To identify optimal liposome formulations for efficient delivery of oligonucleotides into various Candida species.
- To evaluate the efficacy of liposome-mediated oligonucleotide delivery in Candida biofilms and its impact on gene expression and morphology.
Main Methods:
- Dynamic light scattering was employed to characterize and select the most uniform liposome preparations.
- Flow cytometry was utilized to assess the delivery efficiency of fluorescein-labeled oligonucleotides into planktonic Candida albicans, Candida auris, and Candida glabrata.
- Candida biofilms were used to evaluate time-dependent liposome uptake and the delivery of tagged DNA.
Main Results:
- Specific liposome compositions were identified that facilitated optimal delivery of fluorescein-labeled oligonucleotides into planktonic Candida cells.
- Successful delivery of fluorescein-tagged DNA into Candida glabrata biofilms was observed within 24 hours.
- Delivery of antisense-EFG1 via liposomes led to a reduction in Candida albicans hyphal growth and EFG1 gene expression.
Conclusions:
- Commercially available liposomes can effectively facilitate the cellular uptake of antisense oligonucleotides in Candida species.
- Liposome-mediated delivery represents a promising strategy to overcome challenges in treating multidrug-resistant Candida infections.
- This approach holds potential for developing new therapeutic interventions against invasive fungal pathogens.
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