The Catestatin-Derived Peptides Are New Actors to Fight the Development of Oral Candidosis

Abstract

Resistance to antifungal therapy of Candida albicans and non-albicans Candida strains, frequently associated with oral candidosis, is on the rise. In this context, host-defense peptides have emerged as new promising candidates to overcome antifungal resistance. Thus, the aim of this study was to assess the effectiveness against Candida species of different Catestatin-derived peptides, as well as the combined effect with serum albumin. Among Catestatin-derived peptides, the most active against sensitive and resistant strains of C. albicans, C. tropicalis and C. glabrata was the D-isomer of Cateslytin (D-bCtl) whereas the efficiency of the L-isomer (L-bCtl) significantly decreases against C. glabrata strains. Images obtained by transmission electron microscopy clearly demonstrated fungal membrane lysis and the leakage of the intracellular material induced by the L-bCtl and D-bCtl peptides. The possible synergistic effect of albumin on Catestatin-derived peptides activity was investigated too. Our finding showed that bovine serum albumin (BSA) when combined with the L- isomer of Catestatin (L-bCts) had a synergistic effect against Candida albicans especially at low concentrations of BSA; however, no synergistic effect was detected when BSA interacted with L-bCtl, suggesting the importance of the C-terminal end of L-bCts (GPGLQL) for the interaction with BSA. In this context in vitro D-bCtl, as well as the combination of BSA with L-bCts are potential candidates for the development of new antifungal drugs for the treatment of oral candidosis due to Candida and non-Candida albicans, without detrimental side effects.

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“…We also tested the antibacterial activity of D -CTL against E. coli demonstrating that the peptide destabilizes and permeabilizes the bacterial membrane ( 40 ). The antifungal properties of D -CTL were also tested on C. albicans whether sensitive (S) or resistant (R) strains: MIC values were 5.5 µg/mL and 9.6 µg/mL respectively when the L -isoform is active at 50 µg/mL ( 42 ). This improved antimicrobial effect was due to a stronger stability of D -CTL against the proteases released by C. albicans ( 41 ).…”

“…In addition, the D -isoform resists to degradation by enzymes present in saliva ( 41 ). In addition, we tested the same two isoforms of CTL on C. tropicalis (S and R) and C. glabrata (S and R) displaying for all the strains antifungal activity; finally, the highest effect of D -CTL was noticed at a MIC lower than 20 µg/mL ( 42 ).…”

“…Recently, we have demonstrated that CTS, but not CTL, interacts with circulating albumin suggesting the important role of the C terminal part of CTS for the binding ( Figure 1 ). The interaction CTS/albumin improves the antimicrobial activity of the peptide against C. albicans at a concentration of 4 µM, demonstrating a synergistic effect ( 42 ).…”

Antimicrobial Peptides with Anti-Candida Activity

“…This D isomer of cateslytin, which is stable in human saliva, unlike the L isomer, was found to present an additive effect against C. albicans when combined with voriconazole, since the FIC value obtained with the mixture of both antifungal agents was 0.75 [ 98 ]. Recently, the D isomer of bovine cateslytin was reported to be active against C. albicans , C. tropicalis and C. glabrata and was suggested as a possible template for the development of novel treatments for oral candidiasis [ 100 ].…”

Prognostic Value of Catestatin in Severe COVID-19: An ICU-Based Study

“…As aforementioned, catestatin is known for its antimicrobial activity. Several studies investigated catestatin’s potential activity against bacteria, fungi and yeast [ 14 , 25 , 26 ]. Specifically, it has been shown that catestatin’s active domain passes through the cell membrane of microorganisms and accumulates inside the cells [ 14 ].…”