Abstract
The emergence of drug resistance to Candida albicans is problematic in the clinical setting. Therefore, developing new antifungal drugs is in high demand. Our previous work indicated that the antimicrobial peptide P-113Tri exhibited higher antifungal activity against planktonic cells, biofilm cells, and clinical isolates of Candida species compared to its parental peptide P-113. In this study, we further investigated the difference between these two peptides in their mechanisms against C. albicans. Microscopic examination showed that P-113 rapidly gained access to C. albicans cells. However, most of the P-113Tri remained on the cell surface. Moreover, using a range of cell wall-defective mutants and competition assays, the results indicated that phosphomannan and N-linked mannan in the cell wall are important for peptide binding to C. albicans cells. Furthermore, the addition of exogenous phosphosugars reduced the efficacy of the peptide, suggesting that negatively charged phosphosugars also contributed to the peptide binding to the cell wall polysaccharides. Finally, using a glycan array, P-113Tri, but not P-113, can bind to other glycans commonly present on other microbial and mammalian cells. Together, these results suggest that P-113 and P-113Tri have fundamental differences in their interaction with C. albicans and candidacidal activities.
Highlights
Candida species are associated with a range of clinical manifestations, including mucosal and invasive bloodstream infections [1]
P-113Tri Directly Interacts with the Cell Surface of C. albicans
To further investigate the mechanisms of P-113Tri against C. albicans, the interaction between the cells and peptides conjugated with fluorescein isothiocyanate (FITC) was determined using confocal microscopy
Summary
Candida species are associated with a range of clinical manifestations, including mucosal and invasive bloodstream infections [1]. Because there are limited drug classes available for the treatment of Candida infections, and due to the overuse of antifungals, the emergence of drug resistance is becoming a significant concern in clinical settings [2,3]. Because AMPs exhibit broad-spectrum activity against microorganisms and insusceptibility to conventional drug resistance mechanisms, AMPs are promising candidates for the development of new antifungal drugs [9,10,11,12,13]. Compared to P-113, P-113Tri exhibited increased antifungal activity against planktonic cells, biofilm cells, and clinical isolates of C. albicans and non-albicans Candida species [19]. The detailed mechanism by which P-113Tri functions differently from P-113 in its anti-C. albicans activity is still unknown. Our findings suggest the potential use of P-113Tri as a new therapeutic agent that can target the cell wall carbohydrates of fungal pathogens
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