Abstract
Infections caused by invasive fungal biofilms have been widely associated with high morbidity and mortality rates, mainly due to the advent of antibiotic resistance. Moreover, fungal biofilms impose an additional challenge, leading to multidrug resistance. This fact, along with the contamination of medical devices and the limited number of effective antifungal agents available on the market, demonstrates the importance of finding novel drug candidates targeting pathogenic fungal cells and biofilms. In this context, an alternative strategy is the use of antifungal peptides (AFPs) against fungal biofilms. AFPs are considered a group of bioactive molecules with broad-spectrum activities and multiple mechanisms of action that have been widely used as template molecules for drug design strategies aiming at greater specificity and biological efficacy. Among the AFP classes most studied in the context of fungal biofilms, defensins, cathelicidins and histatins have been described. AFPs can also act by preventing the formation of fungal biofilms and eradicating preformed biofilms through mechanisms associated with cell wall perturbation, inhibition of planktonic fungal cells’ adhesion onto surfaces, gene regulation and generation of reactive oxygen species (ROS). Thus, considering the critical scenario imposed by fungal biofilms and associated infections and the application of AFPs as a possible treatment, this review will focus on the most effective AFPs described to date, with a core focus on antibiofilm peptides, as well as their efficacy in vivo, application on surfaces and proposed mechanisms of action.
Highlights
Fungal infections are recurrent in the clinical environment and, annually, affect ∼25% of the general population worldwide, causing high morbidity and mortality rates (Brown et al, 2012; Gamaletsou et al, 2018)
An example of an α-defensin studied for its antifungal actions was human α-defensin 6 (HD6). This peptide demonstrated a blocking action of C. albicans adhesion in human intestinal epithelial cells, and treatment with HD6 at concentrations of 10 or 20 μM resulted in the prevention of biofilm formation (Chairatana et al, 2017)
Plant defensins are stable antifungal peptides (AFPs) with antifungal action and are capable of inhibiting biofilm formation, as well as eradicating preformed biofilms. These AFPs have been proved to act in synergism with conventional antifungal agents, including HsLin06_18 peptide in combination with Csf, which acts on C. albicans biofilm formation (Vriens et al, 2016)
Summary
Fungal infections are recurrent in the clinical environment and, annually, affect ∼25% of the general population worldwide, causing high morbidity and mortality rates (Brown et al, 2012; Gamaletsou et al, 2018). This peptide demonstrated a blocking action of C. albicans adhesion in human intestinal epithelial cells, and treatment with HD6 at concentrations of 10 or 20 μM resulted in the prevention of biofilm formation (Chairatana et al, 2017). A 15-amino acid residue peptide derived from the C-terminus region of the human defensin 3 (HBD3-C15) has revealed antifungal activity in a dose-dependent manner (28.3 – 169.8 μM) against C. albicans biofilm when evaluated on dentin disks (Lim et al, 2016).
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