Host defence peptides identified in human apolipoprotein B as promising antifungal agents

Abstract

Therapeutic options to treat invasive fungal infections are still limited. This makes the development of novel antifungal agents highly desirable. Naturally occurring antifungal peptides represent valid candidates, since they are not harmful for human cells and are endowed with a wide range of activities and their mechanism of action is different from that of conventional antifungal drugs. Here, we characterized for the first time the antifungal properties of novel peptides identified in human apolipoprotein B. ApoB-derived peptides, here named r(P)ApoBLPro, r(P)ApoBLAla and r(P)ApoBSPro, were found to have significant fungicidal activity towards Candida albicans (C. albicans) cells. Peptides were also found to be able to slow down metabolic activity of Aspergillus niger (A. niger) spores. In addition, experiments were carried out to clarify the mechanism of fungicidal activity of ApoB-derived peptides. Peptides immediately interacted with C. albicans cell surfaces, as indicated by fluorescence live cell imaging analyses, and induced severe membrane damage, as indicated by propidium iodide uptake induced upon treatment of C. albicans cells with ApoB-derived peptides. ApoB-derived peptides were also tested on A. niger swollen spores, initial hyphae and branched mycelium. The effects of peptides were found to be more severe on swollen spores and initial hyphae compared to mycelium. Fluorescence live cell imaging analyses confirmed peptide internalization into swollen spores with a consequent accumulation into hyphae. Altogether, these findings open interesting perspectives to the application of ApoB-derived peptides as effective antifungal agents. Key points Human cryptides identified in ApoB are effective antifungal agents. ApoB-derived cryptides exert fungicidal effects towards C. albicans cells. ApoB-derived cryptides affect different stages of growth of A. niger. Graphical abstract

Novel Antimicrobial Strategies to Prevent Biofilm Infections in Catheters after Radical Cystectomy: A Pilot Study

“…However, long-term catheterization increases their risk of complications [ 5 , 6 , 7 ]. In an attempt to assess the antimicrobial efficacy of novel antimicrobial strategies, we analyzed six patient catheter extracts and the effects of the human antimicrobial peptide, i.e., r(P)ApoB L Ala [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. We characterized the composition of catheter-extracted planktonic and adherent communities and evaluated their susceptibility to conventionally prescribed antibiotics, either alone or in combination with the human antimicrobial peptide.…”

“…We have previously characterized the human ApoB-derived antimicrobial peptide’s multifunctional activities (ApoB, residues 887–922), named r(P)ApoB L Ala [ 21 ]. This peptide has antimicrobial and antibiofilm properties and showed synergistic effects in combination with ciprofloxacin, even against clinically isolated bacteria from cystic fibrosis patients [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Worthy of note, the recombinant peptide does not exert toxicity effects on human cell lines, opening the way to many potential biomedical applications.…”

Disclosure of a Promising Lead to Tackle Complicated Skin and Skin Structure Infections: Antimicrobial and Antibiofilm Actions of Peptide PP4-3.1

“…Antimicrobial peptides or, in a broader sense, host defense peptides (HDP), are frontrunners in providing new alternatives to current antibiotics, which are becoming virtually useless against the growing menace of multidrug resistant pathogens. While recent research has unveiled very promising HDP from either natural sources [35][36][37] or recombinant technology [38,39], most of the HDP that have been advanced over the past few years as prospective relevant players in the combat against infectious diseases are of synthetic origin. Rational design, along with chemical synthesis, offers a multiplicity of peptide-based constructs with no match in Nature, enabling a fine tuning of their pharmacodynamic and pharmacokinetic properties, thereby improving their fitness to reach the clinics [40][41][42].…”

DNA Binding Mode Analysis of a Core-Extended Naphthalene Diimide as a Conformation-Sensitive Fluorescent Probe of G-Quadruplex Structures

“…MTT reagent, dissolved in DMEM without phenol red, was added to the cells (100 µL/well) at a final concentration of 0.5 mg/mL. After 4 h at 37 °C, the culture medium was removed and the resulting formazan salts were dissolved by the addition of isopropanol containing 0.1 N HCl (100 µL/well) [ 50 , 51 , 52 ]. Absorbance values of blue formazan were determined at 570 nm by using an automatic plate reader (Synergy™ H4 Hybrid Microplate Reader, BioTek Instruments, Inc., Winooski, VT, USA).…”