2026-07-09 | Combination antifungal therapy against resistant C. albicans: efficacy and immune response in mice.
This study demonstrates the therapeutic effects of combination therapies against Candida albicans in mouse models, as opposed to mono-therapeutic treatments, while also comparing the pathogenicity of both sensitive and resistant strains. Fluconazole-resistant strain of Candida albicans was isolated from an infected patient, and its infectivity potential was compared with a susceptible strain by injecting a fungal cell suspension into the mice model. Additionally, the level of secretory interleukin 17 in the mice was examined. Furthermore, the efficacy of combination therapy was assessed using Fluconazole-Caspofungin (Flu-Cas) and Fluconazole-Amphotericin B (Flu-AmB) in comparison to monotherapy. The results indicate that the resistant strain exhibits higher pathogenicity compared to the susceptible strain in inducing systemic infection within the mouse model, as significant differences between the resistant and susceptible groups were observed at day 5 (p = 0.0401) and day 7 (p = 0.0182). The concentrations of IL-17 (pg/ml) on days 1 to 7 were 43.66 to 259 pg/ml, and 39.66 to 210 pg/ml in resistant and susceptible groups, respectively, which were only significant on days 5 (p = 0.0356) and 7 (p = 0.0280). Combination therapies using Flu-Cas and Flu-AmB demonstrated an effective reduction in fungal colonization after 17 days. This study demonstrates that Fluconazole-resistant Candida albicans strains are more pathogenic than susceptible ones in mice. Combination therapies with Fluconazole-Amphotericin B were most effective in reducing fungal colonization, outperforming monotherapy. These results support combination treatment for resistant Candida infections.
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2026-06-30 | Evaluation of immunological and gene expression responses induced by Galectin-3 and whole-sonicated Candida krusei antigen in rats experimentally infected with Candida krusei.
Candida krusei is an emerging non-Candida albicans species increasingly associated with antifungal resistance and invasive systemic infections. Galectin-3 (GAL-3), a β-galactosidase-binding lectin, and the surfactant protein D gene are important components of innate antifungal immunity. The chemokine (C-X-C motif) ligand-1 gene plays a central role in neutrophil recruitment, whereas whole-sonicated C. krusei antigen may act as a broad fungal immunogen. To evaluate the immunological and pulmonary gene expression responses induced by GAL-3, whole-sonicated C. krusei antigen, and their combination in rats experimentally infected with C. krusei, via measurement of serum immunoglobulin G, interleukin-17, interleukin-23, and lung expression of Chemokine (C-X-C motif) ligand 1 (CXCL-1) and surfactant protein D genes. A total of 120 rats were randomly allocated into four experimental groups (n = 30). Animals received GAL-3, whole-sonicated C. krusei antigen, and their combination, while the control group was subdivided into infected and healthy controls. Immunized groups were administered subcutaneously according to the experimental schedule. Systemic C. krusei infection was induced intraperitoneally, and samples were collected at 15 and 30 days post-challenge. Serum Immunoglobulin G, Interleukin -17 (IL-17), and Interleukin -23 (IL-23) levels were measured using ELISA. Pulmonary CXCL-1 and surfactant protein D gene expression were quantified using SYBR Green reverse transcription quantitative polymerase chain reaction and analyzed using the 2⁻ΔΔCt method. Immunoglobulin G levels increased significantly in all treated groups compared with infected and healthy controls, with the highest levels at day 30. Whole-sonicated C. krusei antigen and mixed treatment groups showed significant increases in IL-17 and IL-23, indicating activation of Th17-mediated immune responses. Galectin-3 treatment produced upregulation of CXCL-1 and surfactant protein D genes, whereas the antigen-treated group showed moderate gene expression changes. The combined treatment group demonstrated reduced CXCL-1 induction but maintained a modest increase in surfactant protein D expression. Galectin-3 and whole-sonicated C. krusei antigen may enhance antifungal immune responses through partially distinct mechanisms. Galectin-3 modulates the CXCL-1 and surfactant protein D gene axis and activate innate immune pathways, whereas whole-sonicated antigen stimulates IL-23/IL-17-mediated responses and humoral immunity. These findings suggest that GAL-3 and fungal antigen immunization may represent support immunomodulatory approaches for controlling infections caused by non-C. albicans.
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2026-06-26 | Prophylactic potential of Astragalus membranaceus extract in experimental pulmonary Candidiasis in Albino rats.
Invasive candidiasis is a fungal infection with potentially serious outcomes, requiring novel therapies to overcome drug resistance. Astragalus membranaceus (AM) dried root extract has been shown to have anti-inflammatory and immunomodulatory properties. This study aimed to examine the anticandidal potential of AM versus fluconazole and explore the mechanisms underlying the antifungal effect in a model of lung candidiasis. Four groups (n = 6, in each) of twenty-four mature male Wistar albino rats were created: non-infected control, Candida-infected, AM-treated, and fluconazole-treated groups. Lung candidiasis was induced by a single intravenous inoculation of Candida albicans on the 10th day. In AM- and fluconazole-treated groups, the infected rats received AM extract (1000 mg/kg/day) and fluconazole (10 mg/kg/day) orally for 11 days. On day 12, the animals were sacrificed, and the lung tissues were harvested for microbiological, biochemical, and histological analyses. Lung tissue homogenates were subjected to ELISA and polymerase chain reaction (PCR)-based measurement of IL-1β, IL-4, IL-6, IL-10, IL-12, and TNF-α. Also, immunohistochemistry of NF-κB and i-NOS was conducted. In vitro evaluation using disc diffusion and minimum inhibitory concentration assays were used to evaluate AM's antifungal efficacy. AM improved lung histology, reduced the pulmonary fungal load, decreased lung cytokine levels, and increased the lung tissue levels of IL-12, compared to the infected group. Also, AM increased the iNOS expression at gene and protein levels, meanwhile downregulated NF-κB, in comparison with the infected group. In summary, AM protected against the lung damage caused by Candida, possibly by modulating the inflammatory response and NF-κB/IL-12/iNOS signaling pathway.
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