The antifungal activity of aspirin against cryptococcal cells has been reported. However, the unwanted effects of aspirin may limit its clinical application. Conceivably, a derivative of aspirin could overcome this challenge. Toward this end, this study considered the usage of an aspirinate-metal complex, namely, copper acyl salicylate (CAS), as an anti- antifungal agent. Additionally, the study examined the effects of this compound on macrophage function. The susceptibility results revealed that cryptococcal cells were vulnerable (in a dose-dependent manner) to CAS, which might have effected growth inhibition by damaging cryptococcal cell membranes. Interestingly, when CAS was used in combination with fluconazole or amphotericin B, synergism was observed. Furthermore, CAS did not negatively affect the growth or metabolic activity of macrophages; rather, it sensitized those immune cells to produce interferon gamma and interleukin 6, which, in turn, might have aided in the phagocytosis of cryptococcal cells. Compared to our aspirin data, CAS was noted to be more effective in killing cryptococcal cells (based on susceptibility results) and less toxic toward macrophages (based on growth inhibition results). Taking these findings together, it is reasonable to conclude that CAS may be a better anti- drug that could deliver better therapeutic outcomes, compared to aspirin.
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http://dx.doi.org/10.1128/AAC.02345-17 | DOI Listing |
Nat Prod Res
December 2024
School of Science, Walailak University, Thasala, Nakhonsithammarat, Thailand.
Two new compounds including one benzaldehyde () and one azaphilone () were isolated from the marine-derived fungus PSU-AMF89 together with nine known compounds (-). Their structures were determined by spectroscopic evidences. The absolute configuration of was established by comparison of the ECD data with those of the previously reported data of compound as well as the biosynthetic consideration.
View Article and Find Full Text PDFInfect Immun
December 2024
Laboratory of Applied Immunology, Institute of Biology Sciences, University of Brasília, Brasília, Brazil.
Dormancy is an adaptation in which cells reduce their metabolism, transcription, and translation to stay alive under stressful conditions, preserving the capacity to reactivate once the environment reverts to favorable conditions. Dormancy and reactivation of () are closely linked to intracellular residency within macrophages. Our previous work showed that murine macrophages rely on the viable but not cultivable (VBNC-a dormancy phenotype) fungus from active , with striking differences in immunometabolic gene expression.
View Article and Find Full Text PDFPLoS One
December 2024
Department of Genetics and Biochemistry, Eukaryotic Pathogens Innovation Center, Clemson University, Clemson, SC, United States of America.
Cryptococcus neoformans is a pathogenic basidiomycetous yeast that primarily infects immunocompromised individuals. Fatal outcome of cryptococcosis depends on the ability of C. neoformans to sense and adapt to 37°C.
View Article and Find Full Text PDFHeliyon
December 2024
Department of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China.
Objective: To investigate the mechanism underlying the regulation of blood-brain barrier permeability changes during cryptococcal meningitis by NLRP3 and Vimentin.
Methods: Sprague-Dawley rats were treated with WT Cryptococcus neoformans (Cn) or CPS1-/- Cn. Neuronal apoptosis was assessed using TUNEL staining, and pathological changes were observed using electron microscopy and HE staining.
Unlabelled: is a fungal pathogen that can cause lethal disease in immunocompromised patients. Immunocompetent host immune responses, such as formation of pulmonary granulomas, control the infection and prevent disseminated disease. Little is known about the immunological conditions establishing the latent infection granuloma in the lungs.
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