Inhibition of Candida albicans growth by brominated furanones.
Candida albicans is the most virulent Candida species of medical importance, which presents a great threat to immunocompromised individuals such as HIV patients. Currently, there are only four classes of antifungal agents available for treating fungal infections: azoles, polyenes, pyrimidines, and echinocandins. The fast spread of multidrug resistant C. albicans strains has increased the demand for new antifungal drugs. In this study, we demonstrate the antifungal activity of brominated furanones on C. albicans. Studying the structure and activity of this class of furanones reveals that the exocyclic vinyl bromide conjugated with the carbonyl group is the most important structural element for fungal inhibition. Furthermore, gene expression analysis using DNA microarrays showed that 3 microg/mL of 4-bromo-5Z-(bromomethylene)-3-butylfuran-2-one (BF1) upregulated 32 C. albicans genes with functions of stress response, NADPH dehydrogenation, and small-molecule transport, and repressed 21 genes involved mainly in cell-wall maintenance. Interestingly, only a small overlap is observed between the gene expression changes caused by the representative brominated furanone (BF1) in this study and other antifungal drugs reported in literature. This result suggests that brominated furanones and other antifungal drugs may target different fungal proteins or genes. The existence of such new targets provides an opportunity for developing new agents to control fungal pathogens which are resistant to currently available drugs.
Duo
Miao
M
Department of Civil and Environmental Engineering, Syracuse University, Syracuse, NY 13244, USA.
Zhang
Mi
M
Luk
Yan-Yeung
YY
Ren
Dacheng
D
D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D025141:Drug Resistance, Fungal; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D005663:Furans / Q000737:chemistry / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D020411:Oligonucleotide Array Sequence Analysis
C548494:4-bromo-5Z-(bromomethylene)-3-butylfuran-2-one; D000935:Antifungal Agents; D001393:Azoles; D005656:Fungal Proteins; D005663:Furans; D006842:Hydrocarbons, Brominated