Biology subjects

Szweda, P.

Publications and source records attributed to Szweda, P..

3 recordsLinked to original sources

bioRxiv2026

Deciphering the antifungal mechanism of Polish ethanolic extracts of propolis against Candida albicans: Evidence for a multi-target mode of action

Propolis, a resinous product of plant origin collected by honeybees, has long been used in traditional medicine for its antimicrobial properties. However, its antifungal mechanism of action against Candida albicans remains incompletely understood. This study aimed to elucidate the antifungal mechanism of ethanolic extracts of Polish propolis (EEP) and a defined mixture of its key flavonoid constituents against C. albicans. Antifungal activity was assessed using Time-kill assay and broth microdilution method under different medium supplementation conditions. Cellular responses were analysed by fluorescence microscopy (FM) and flow cytometry (FCM) in regard to: membrane integrity, reactive oxygen species (ROS) accumulation, mitochondrial membrane potential changes, cytosolic Ca{superscript 2} levels, and morphological transition. Transcriptomic changes were evaluated by RNA sequencing (RNA-seq) and validated by quantitative reverse transcription PCR (RT-qPCR). EEP exhibited concentration-dependent, extract-specific antifungal activity, with selected samples showing rapid fungicidal effects. Mechanistic studies demonstrated membrane permeabilization, reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, disruption of Ca{superscript 2} homeostasis, and inhibition of hyphal formation. Ergosterol supplementation reduced antifungal efficacy, indicating membrane sterols as primary targets. Transcriptomic analysis revealed downregulation of genes associated with DNA replication, transcription, and biosynthesis, alongside upregulation of stress-response pathways, including oxidative stress, protein folding, and mitochondrial processes. Polish propolis exerts antifungal activity through a multi-target mechanism involving membrane disruption and induction of cellular stress. Transcriptomic data indicate coordinated suppression of essential cellular functions and activation of stress-response pathways, supporting a system-level disruption of fungal homeostasis.

microbiology↗

bioRxiv2026

Ethanolic Extract of Polish Propolis exhibits synergy with selected antifungal agents against yeast pathogens causing candidiasis

Candidiasis pose a serious health threat, stimulating efforts to develop new antifungal agents and alternative therapies. Given the high mortality of fungal infections and the historical use of natural remedies, there is a growing interest in integrating natural substances into modern treatments. It is particularly important to explore interactions between home remedies and clinically approved antifungals to avoid harmful combinations or enhance beneficial effects. In this study, the chemical composition of the ethanolic extract of propolis (EEP) using UHPLC-DAD-QqTOF-MS was analyzed. The interactions of this extract with several antifungal agents against four yeast pathogens causing candidiasis: Candida albicans, Nakaseomyces glabratus, Pichia kudriavzevii, and Candida auris were investigated using Checkerboard Titration Assay, Growth Kinetics, and Disc-diffusion assay. Also, a novel simulated infection model was proposed. The results showed synergistic interactions between EEP and amphotericin B, and additive effects with nystatin. Synergy and additivity with fluconazole and voriconazole were observed, but limited to C. albicans and N. glabratus. In contrast, antagonistic interactions were noted with caspofungin, clotrimazole, and ketoconazole, which may have clinical relevance. Additionally, positive interactions with 2-phenoxyethanol and silver nanoparticles (AgNPs) suggest potential practical applications. Propoliss synergistic properties could expand antifungal strategies and support the development of multi-target, resistance-preventing therapies.

microbiology↗

bioRxiv2024

Afterload-induced Decreases in Fatty Acid Oxidation Develop Independently of Increased Glucose Utilization

BackgroundMetabolic substrate utilization in HFpEF (heart failure with preserved ejection fraction), the leading cause of heart failure worldwide, is pivotal to syndrome pathogenesis and yet remains ill defined. Under resting conditions, oxidation of free fatty acids (FFA) is the predominant energy source of the heart, supporting its unremitting contractile activity. In the context of disease-related stress, however, a shift toward greater reliance on glucose occurs. In the setting of obesity or diabetes, major contributors to HFpEF pathophysiology, the shift in metabolic substrate use toward glucose is impaired, sometimes attributed to the lower oxygen requirement of glucose oxidation versus fat metabolism. This notion, however, has never been tested conclusively. Furthermore, whereas oxygen demand increases in the setting of increased afterload, myocardial oxygen availability remains adequate for fatty acid oxidation (FAO). Therefore, a "preference" for glucose has been proposed. Methods and ResultsPyruvate dehydrogenase complex (PDC) is the rate-limiting enzyme linking glycolysis to the TCA cycle. As PDK4 (PDC kinase 4) is up-regulated in HFpEF, we over-expressed PDK4 in cardiomyocytes, ensuring that PDC is phosphorylated and thereby inhibited. This leads to diminished use of pyruvate as energy substrate, mimicking the decline in glucose oxidation in HFpEF. Importantly, distinct from HFpEF-associated obesity, this model positioned us to abrogate the load-induced shift to glucose utilization in the absence of systemic high fat conditions. As expected, PDK4 transgenic mice manifested normal cardiac performance at baseline. However, they manifested a rapid and severe decline in contractile performance when challenged with modest increases in afterload triggered either by L-NAME or surgical transverse aortic constriction (TAC). This decline in function was not accompanied by an exacerbation of the myocardial hypertrophic growth response. Surprisingly, metabolic flux analysis revealed that, after TAC, fractional FAO decreased, even when glucose/pyruvate utilization was clamped at very low levels. Additionally, proteins involved in the transport and oxidation of FFA were paradoxically downregulated after TAC regardless of genotype. ConclusionsThese data demonstrate that cardiomyocytes in a setting in which glucose utilization is robustly diminished and prevented from increasing do not compensate for the deficit in glucose utilization by up-regulating FFA use.

cell biology↗