DS6: anticandidal, antibiofilm peptide against Candida tropicalis and exhibit synergy with commercial drug

Abstract

Antifungal peptides have gained interest as therapeutic agents in recent years because of increased multidrug resistance against present antifungal drugs. This study designed, synthesized and characterized antifungal activity of a small peptide analogue, DS6. This peptide was designed using the template from the N-terminal part of the antifungal protein, Aspergillus giganteous. DS6 inhibited Candida tropicalis (ATCC 13803), as well as its clinical isolates. DS6 was found to be a fungicidal, killing the fungus very rapidly. DS6 is also non-toxic to human cells. Synergistic interactions of DS6 with amphotericin B and fluconazole were also evident. DS6 is membrane lytic and exhibits antibiofilm activity against C. tropicalis. In conclusion, DS6 may have utility as an alternative antifungal therapy for C. tropicalis. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Antimicrobial Susceptibility Testing of Antimicrobial Peptides to Better Predict Efficacy

“…A large number of publications have described in vitro synergy of selected AMP with other AMP (Zerweck et al, 2017 ; Hanson et al, 2019 ), antibiotics (for example Cassone and Otvos, 2010 ; Sakoulas et al, 2014 ; Soren et al, 2015 ; Pollini et al, 2017 ; Pizzolato-Cezar et al, 2019 ) or antifungals (Duggineni et al, 2007 ; Singh et al, 2017 ), although this is not always the case (He et al, 2015 ) and is something that is no doubt under-reported. Conjugates of AMP and antibiotics, organometallic compounds, gold nanoparticles or to create AMP polymers to increase efficacy, to reduce toxicity and/or to improve formulation have become of increasing interest over recent years (for examples, see Reinhardt and Neundorf, 2016 ; Rajchakit and Sarojini, 2017 ; David et al, 2018 ; Sun et al, 2018 ) and will undoubtedly require additional consideration when it comes to AST.…”

Antimicrobial activity of denture adhesive associated with Equisetum giganteum- and Punica granatum-enriched fractions against Candida albicans biofilms on acrylic resin surfaces

“…Therefore, in association with proper oral and denture hygiene, DS treatment may involve the prescription of topical and/or systemic conventional antifungal agents (Bueno et al 2015). Due to their high oral bioavailability and easy access to conventional antifungal agents, medications such as nystatin and fluconazole have been widely used to treat pathologies where C. albicans is the main causal factor (Ng et al 2017;Singh et al 2017).…”

Antimicrobial Peptide Synergies for Fighting Infectious Diseases

“…[223] The DS6 peptide was found to be synergistic with amphotericin B against both the clinical isolates and ATCC 13803 with FICI 0.5 and 0.37, respectively. [204] Lactoferrin-derived peptide used in combination with amphotericin B is synergistic in both Candida species (FICI = 0.375) and C. neoformans (FICI = 0.5) but indifferent in C. deuterogattii (FICI = 0.75). [224] The combination of synthetic pilosulin-(Dq-2562, Dq-1503, and Dq-1319) and ponericin-like (Dq-3162) peptides and conventional antimycotic drugs, including amphotericin B, displays a synergistic reduction in the MIC values of individual peptides and drugs, in which underlying mechanism of action involves membrane disruption of Candida spp.…”

“…[202,203] The DS6 peptide was found to be synergistic with fluconazole against Candida species. [204] The peptide Cc-GRP at 400 μg mL −1 in combination with fluconazole at 20 μg mL −1 was reported to inhibit the growth of the fungus Fusarium solani, promote the permeabilization of its membrane, and induce the production of ROS, thereby suggesting synergistic activity between the peptide and fluconazole. [205] The human cathelicidin LL-37:fluconazole combination at a 1:1 ratio results in 70% synergy against C. auris.…”

“…[ 223 ] The DS6 peptide was found to be synergistic with amphotericin B against both the clinical isolates and ATCC 13803 with FICI 0.5 and 0.37, respectively. [ 204 ] Lactoferrin‐derived peptide used in combination with amphotericin B is synergistic in both Candida species (FICI = 0.375) and C. neoformans (FICI = 0.5) but indifferent in C. deuterogattii (FICI = 0.75). [ 224 ]…”