Abstract
The interaction of positively charged polymers (polycations) with a biological membrane is considered to be the cause of the frequently observed toxicity of these macromolecules. If it is possible to obtain polymers with a predominantly negative effect on bacterial and fungal cells, such systems would have great potential in the treatment of infectious diseases, especially now when reports indicate the growing risk of fungal co-infections in COVID-19 patients. We describe in this article cationic derivatives of natural beta-glucan polymers obtained by reacting the polysaccharide isolated from Saccharomyces boulardii (SB) and Cetraria islandica (CI) with glycidyl trimethyl ammonium chloride (GTMAC). Two synthesis strategies were applied to optimize the product yield. Fungal diseases particularly affect low-income countries, hence the emphasis on the simplicity of the synthesis of such drugs so they can be produced without outside help. The three structures obtained showed selective anti-mycotic properties (against, i.e., Scopulariopsis brevicaulis, Aspergillus brasiliensis, and Fusarium solani), and their toxicity established using fibroblast 3T3-L1 cell line was negligible in a wide range of concentrations. For one of the polymers (SB derivative), using in vivo model of Aspergillus brasiliensis infection in Galleria mellonella insect model, we confirmed the promising results obtained in the preliminary study.
Highlights
In the case of S. boulardii (SB), containing more proteins, a negligible amount of nitrogen remained in the final material used for cationization, which may indicate a marginal quantity of proteins remaining in the sample
After 2 h incubation at 37 ◦ C, the larvae were randomly divided into three groups (10 larvae per group) and injected with 3 μL of insect physiological saline (IPS) or 3 μL of SBBGTMAC2 solution in IPS
Our research on antifungal activity of cationic beta-glucan derivatives indicates that these substances exhibit selective antifungal activity against certain species
Summary
Fungal infections are one of the most common diseases affecting people all over the world. Fungi are responsible for over a billion infections globally and cause more than 1.5 million deaths worldwide [1]. Most people during their lifetime will suffer from superficial or mucocutaneous fungal infections, which generally do not have serious health consequences but often significantly reduce the quality of life. It is related to the progress of medicine, which allows patients with serious underlying diseases to be kept alive, contributing directly or as a result of therapy to increased susceptibility to mycoses (e.g., HIV infection and AIDS, iatrogenic immunosuppression, invasive medical procedures, antibiotic therapy, steroid therapy, diabetes mellitus)
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