Novel Arginine- and Proline-Rich Candidacidal Peptides Obtained through a Bioinformatic Approach

Abstract

Antimicrobial resistance is a major public health concern worldwide. Albeit to a lesser extent than bacteria, fungi are also becoming increasingly resistant to antifungal drugs. Moreover, due to the small number of antifungal classes, therapy options are limited, complicating the clinical management of mycoses. In this view, antimicrobial peptides (AMPs) are a potential alternative to conventional drugs. Among these, Proline-rich antimicrobial peptides (PrAMPs), almost exclusively of animal origins, are of particular interest due to their peculiar mode of action. In this study, a search for new arginine- and proline-rich peptides from plants has been carried out with a bioinformatic approach by sequence alignment and antimicrobial prediction tools. Two peptide candidates were tested against planktonic cells and biofilms of Candida albicans and Candida glabrata strains, including resistant isolates. These peptides showed similar potent activity, with half-maximal effective concentration values in the micromolar range. In addition, some structural and functional features, revealing peculiar mechanistic behaviors, were investigated.

Adsorption/Desorption of Cationic-Hydrophobic Peptides on Zwitterionic Lipid Bilayer Is Associated with the Possibility of Proton Transfer

“…The adsorption of R5F2/K5F2 on DPPC′ is reflected in the alternations of DPPC′ thermotropic properties, but calorimetric and spectrophotometric data were demonstrated to be inconsistent and, at this very moment, it does not seem possible to state whether peptide adsorption contributes to the rigidity or softening of lipid bilayers. From a molecular-level point of view, it is unequivocally demonstrated that when Ultimately, the findings provided in this research should not be limited only to the context of Arg-and Lys-rich peptides as CPPs; they may also open the way of understanding the mode of action of intrinsically neuroprotective Arg-rich peptides [60][61][62] and their antifungal potential [63], while their fundamental differences in adsorption/desorption processes might help to explain the stronger antiviral activity of Arg-rich compared to Lys-rich peptides [64,65].…”

“…These proton transfer-related opposites might be mirrored in different trends of phase transition temperatures (Tpt) of DPPC′ when interacting with R5F2/K5F2 (see Table 1), and a more detailed explanation of the observed phenomena will be provided in a subsequent work. Ultimately, the findings provided in this research should not be limited only to the context of Arg-and Lys-rich peptides as CPPs; they may also open the way of understanding the mode of action of intrinsically neuroprotective Arg-rich peptides [60][61][62] and their antifungal potential [63], while their fundamental differences in adsorption/desorption processes might help to explain the stronger antiviral activity of Arg-rich compared to Lysrich peptides [64,65].…”

Antifungal Efficacy of Antimicrobial Peptide Octominin II against Candida albicans

“…Although AMPs are readily found in natural sources, their use in therapeutics is not feasible. Researchers have focused more on synthetic peptides because they can be easily designed, modified, and synthesized in large quantities with high purity, and the activity of AMPs can be predetermined using bioinformatic tools coupled with machine learning [ 12 , 13 ]. Promising AMPs have been developed using defense protein sequences from various organisms [ 14 , 15 , 16 , 17 , 18 , 19 ].…”