Abstract
BACKGROUND: Diabetes mellitus renders patients susceptible to chronic wounds and fungal infections, such as Candida albicans infections. The treatment of C. albicans-infected diabetic wounds is often problematic due to drug resistance and biofilm formation. Therefore, we studied the impact of β-carotene on treating diabetic wounds infected with strong biofilm-forming multidrug-resistant (MDR) C. albicans. RESULTS: Our data showed that β-carotene (200 µg/ml) exhibited potent antifungal activity against the planktonic C. albicans cells, including MDR cells, with inhibition zones of 14 to 34 mm, which was emphasized by methylene blue staining and growth kinetics analysis. Using polystyrene plates and silicon catheter models, β-carotene showed a promising antibiofilm action by disrupting the established biofilms of C. albicans by 95% and 75.9%, respectively, which was confirmed by crystal violet staining, dual staining, and fluorescence staining approaches. The antibiofilm pathway of β-carotene was also examined, and it was found that β-carotene targeted the first stage of biofilm via reducing the adherence up to 90%, which was linked to downregulation of expression of the hypha-specific gene, ALS3, and blocking action of agglutinin-like protein 3 (Als3) via complexation (-9.8 kcal/mol). In addition, β-carotene disrupted the initiation step by inhibiting the yeast-to-hyphae transition and lowering the viability of sessile cells up to 80%. Furthermore, the maturation step of biofilm was embattled by β-carotene through a 95.6% reduction in the production of polysaccharide matrix. The in vivo model demonstrated the curative role of β-carotene in the healing process, which displayed a wound healing ratio of 89%, a lower fungal burden, and better histological features. CONCLUSION: Our findings demonstrated the therapeutic potential of β-carotene for treating diabetic wounds infected with strong biofilm-forming MDR C. albicans.