Abstract
Resistance of the opportunistic pathogen Candida albicans to antifungal drugs has increased significantly in recent years. After screening 55 potential antifungal compounds from a chemical library, 2,3-dihydroxy-4-methoxybenzaldehyde (DHMB) was identified as having potential antifungal activity. The properties of DHMB were then assessed in vitro and in vivo against C. albicans overgrowth and intestinal inflammation. Substitution on the aromatic ring of DHMB led to a strong decrease in its biological activity against C. albicans. The MIC of DHMB was highly effective at eliminating C. albicans when compared to that of caspofungin or fluconazole. Additionally, DHMB was also effective against clinically isolated fluconazole- or caspofungin-resistant C. albicans strains. DHMB was administered to animals at high doses. This compound was not cytotoxic and was well-tolerated. In experimental dextran sodium sulphate (DSS)-induced colitis in mice, DHMB reduced the clinical and histological score of inflammation and promoted the elimination of C. albicans from the gut. This finding was supported by a decrease in aerobic bacteria while anaerobic bacteria populations were re-established in mice treated with DHMB. DHMB is a small organic molecule with antifungal properties and anti-inflammatory activity by exerting protective effects on intestinal epithelial cells.
Highlights
Inflammatory bowel diseases (IBDs), comprising Crohn’s disease (CD) and ulcerative colitis, have a multifactorial aetiology with complex interactions between genetic susceptibility, the immune system, environment and the microbiota [1]
The biodiversity of the gut microbiota is frequently decreased in IBD patients, in particular a reduction in Firmicutes and an increase in Proteobacteria are often observed [2]
Escherichia coli is part of the Proteobacteria phylum and is increased greatly while Lactobacillus species belonging to the Firmicutes phylum are reduced in IBD patients [3,4]
Summary
Inflammatory bowel diseases (IBDs), comprising Crohn’s disease (CD) and ulcerative colitis, have a multifactorial aetiology with complex interactions between genetic susceptibility, the immune system, environment and the microbiota [1]. The biodiversity of the gut microbiota is frequently decreased in IBD patients, in particular a reduction in Firmicutes and an increase in Proteobacteria are often observed [2]. In an experimental murine model of dextran sodium sulphate (DSS)-induced colitis, the population of aerobic bacteria, in particular E. coli and Enterococcus faecalis, increased, whereas the population of anaerobic bacteria such as Lactobacillus johnsonii and Bifidobacterium species decreased. These microbiota modifications were associated with overgrowth of fungi suggesting that dysbiosis could play a crucial role in IBD [9]. We assessed the in vitro and in vivo antifungal properties of a novel compound, 2,3-dihydroxy-4-methoxybenzaldehyde (DHMB), against C. albicans colonisation and intestinal inflammation
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