Antimicrobial Peptides: a New Frontier in Antifungal Therapy

Abstract

Invasive fungal infections in humans are generally associated with high mortality, making the choice of antifungal drug crucial for the outcome of the patient. The limited spectrum of antifungals available and the development of drug resistance represent the main concerns for the current antifungal treatments, requiring alternative strategies. Antimicrobial peptides (AMPs), expressed in several organisms and used as first-line defenses against microbial infections, have emerged as potential candidates for developing new antifungal therapies, characterized by negligible host toxicity and low resistance rates. Most of the current literature focuses on peptides with antibacterial activity, but there are fewer studies of their antifungal properties. This review focuses on AMPs with antifungal effects, including their in vitro and in vivo activities, with the biological repercussions on the fungal cells, when known. The classification of the peptides is based on their mode of action: although the majority of AMPs exert their activity through the interaction with membranes, other mechanisms have been identified, including cell wall inhibition and nucleic acid binding. In addition, antifungal compounds with unknown modes of action are also described. The elucidation of such mechanisms can be useful to identify novel drug targets and, possibly, to serve as the templates for the synthesis of new antimicrobial compounds with increased activity and reduced host toxicity.

Microbial Interkingdom Biofilms and the Quest for Novel Therapeutic Strategies

“…The main advantages are broad-spectrum activity, relatively low toxicity, rapid mechanism of action, and low probability of antimicrobial resistance. Several studies showed that AMPs can target bacteria and fungi by interacting with microbial membranes and disrupting the physical integrity [ 103 , 104 ]. However, the potential to use AMPs against polymicrobial infections has only been explored recently.…”

Permeation eines 5.1‐kDa‐Peptides durch einen Proteinkanal: Molekulare Basis der Translokation von Protamin durch CymA aus Klebsiella Oxytoca**

“…All simulations were performed using the GROMACS 2019.4 package [14] with the CHARMM36 force field. [15] The figures were generated using VMD. [16] The remaining simulation parameters were the same as in our previous study.…”

“…[6,7] Typical examples are cationic antimicrobial peptides that have attracted wider interest as substitutes for classical antibiotics. [8][9][10][11][12][13][14][15][16] Whether these polycationic peptides permeate using a self-promoted pathway or through channel proteins remains an open but crucial question in understanding their antimicrobial activity and other putative functions. One such molecule is protamine (Ptm) which is a 32 amino acid-long polycationic peptide with a molecular mass of 5.1 kDa that contains 21 arginine residues ( Figure 1A).…”

“…[6,7] Ty pische Beispiele sind kationische antimikrobielle Peptide,d ie als Ersatz fürk lassische Antibiotika ein breiteres Interesse gefunden haben. [8][9][10][11][12][13][14][15][16] Ob diese polykationischen Peptide über einen selbstfçrdernden Wego der über Kanalproteine eindringen, ist eine offene,aber entscheidende Frage zum Verständnis ihrer antimikrobiellen Aktivität. Ein solches Moleküli st Protamin (Ptm), ein 32 Aminosäuren langes polykationisches Peptid mit einer Molekülmasse von 5,1 kDa, welches 21 Argininreste enthält (Abbildung 1A).…”

Large‐Peptide Permeation Through a Membrane Channel: Understanding Protamine Translocation Through CymA from Klebsiella Oxytoca**

“…[6,7] Ty pical examples are cationic antimicrobial peptides that have attracted wider interest as substitutes for classical antibiotics. [8][9][10][11][12][13][14][15][16] Whether these polycationic peptides permeate using as elf-promoted pathway or through channel proteins remains an open but crucial question in understanding their antimicrobial activity and other putative functions.O ne such molecule is protamine (Ptm) which is a32amino-acid-long polycationic peptide with amolecular mass of 5.1 kDa that contains 21 arginine residues ( Figure 1A). This molecule is ac heap byproduct from fish industry and used as an antibiotic in fish farming.…”