Synergistic Antifungal Activity of Synthetic Peptides and Antifungal Drugs against Candida albicans and C. parapsilosis Biofilms

Abstract

C. albicans and C. parapsilosis are biofilm-forming yeasts responsible for bloodstream infections that can cause death. Synthetic antimicrobial peptides (SAMPs) are considered to be new weapons to combat these infections, alone or combined with drugs. Here, two SAMPs, called Mo-CBP3-PepI and Mo-CBP3-PepIII, were tested alone or combined with nystatin (NYS) and itraconazole (ITR) against C. albicans and C. parapsilosis biofilms. Furthermore, the mechanism of antibiofilm activity was evaluated by fluorescence and scanning electron microscopies. When combined with SAMPs, the results revealed a 2- to 4-fold improvement of NYS and ITR antibiofilm activity. Microscopic analyses showed cell membrane and wall damage and ROS overproduction, which caused leakage of internal content and cell death. Taken together, these results suggest the potential of Mo-CBP3-PepI and Mo-CBP3-PepIII as new drugs and adjuvants to increase the activity of conventional drugs for the treatment of clinical infections caused by C. albicans and C. parapsilosis.

A Novel Peptide with Antifungal Activity from Red Swamp Crayfish Procambarus clarkii

“…On the contrary, the synthetic peptide #14d did not cause ROS overproduction in C. albicans ATCC 10231 biofilm, which are involved in the disruption of essential molecules such as proteins, lipids, and DNA. This result corroborates those reported by Bezerra and collaborators [ 43 ], who showed the absence of ROS overproduction by C. albicans biofilm after treatments with the conventional antifungal agents nystatin and itraconazole. MD simulations performed on this peptide further suggested that the displayed antifungal activity could be partially related to the overall wide distribution of the positive electrostatic charge in its three-dimensional structure.…”

“…Of particular importance, the synthetic derivative peptide #14d (FHLVWRAGGTF), selected on the basis of three advantageous chemical-physical parameters (percentage of hydrophobic ratio, charge, Boman index), due to its interesting antifungal activity and low toxicity toward human cells in vitro, may represent a good therapeutic candidate worthy to be developed against the pathogen C. albicans . Peptide #14d inhibited the growth of C. albicans ATCC 10231 through cell membrane damage causing death [ 41 , 42 , 43 ]. The peptide showed indicative anticandidal activity, revealing a MIC value equal to 31.2 μg/mL.…”

“…The cell membrane integrity of C. albicans ATCC 10231 after exposure to peptide #14d was evaluated using the PI uptake assay, as described by Bezerra et al [ 43 ], with some modifications. C. albicans ATCC 10231 was incubated with the peptide #14d in the same conditions reported for inhibition of biofilm formation.…”

“…The morphological changes in C. albicans ATCC 10231 cells were assessed by scanning electron microscopy (SEM, Phenom ProX, PhenomWorld, Eindhoven, Netherlands), using the method described by Bezerra et al [ 43 ], with some modifications. Biofilms were fixed with a 4% formaldehyde solution in DPBS for 30 min at 37 °C.…”

Giving a Hand: Synthetic Peptides Boost the Antifungal Activity of Itraconazole against <em>Cryptococcus Neoformans</em>

“…Recently, synthetic antimicrobial peptides have emerged as potential candidates because they are based on natural antimicrobial peptides but have high activity and low toxicity levels [5][6][7]. In addition to being employed alone, synthetic peptides could be applied synergistically with commercial drugs to improve their action [8][9][10][11]. For Disclaimer/Publisher's Note: The statements, opinions, and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s).…”