Membrane-Interacting Antifungal Peptides

Abstract

The incidence of invasive fungal infections is increasing worldwide, resulting in more than 1.6 million deaths every year. Due to growing antifungal drug resistance and the limited number of currently used antimycotics, there is a clear need for novel antifungal strategies. In this context, great potential is attributed to antimicrobial peptides (AMPs) that are part of the innate immune system of organisms. These peptides are known for their broad-spectrum activity that can be directed toward bacteria, fungi, viruses, and/or even cancer cells. Some AMPs act via rapid physical disruption of microbial cell membranes at high concentrations causing cell leakage and cell death. However, more complex mechanisms are also observed, such as interaction with specific lipids, production of reactive oxygen species, programmed cell death, and autophagy. This review summarizes the structure and mode of action of antifungal AMPs, thereby focusing on their interaction with fungal membranes.

Antimicrobial Peptides in Gut Health: A Review

“…Some studies have found that the intracellular targets can be affected by AMPs though ROS production, programmed cell death, mitochondrial dysfunction, disruption of cation homeostasis, ATP efflux, cell cycle impairment, autophagy, and vacuolar dysfunction. AMPs, which finish interacting with the target, can be internalized or can remain outside the fungal cell ( 35 ).…”

Short Peptides Make a Big Difference: The Role of Botany-Derived AMPs in Disease Control and Protection of Human Health

“…Pathogenic fungi are considered a greater threat to plant and animal biodiversity than other taxonomic classes [ 101 ]. As part of the intrinsic immune system, BAMPs have great potential to be developed as novel antifungal agents due to their broad-spectrum activity, selective targeting, multiple mechanisms of action, and limited cell cytotoxicity [ 7 , 102 ]. Elucidating the functional mechanism of BAMPs is key to uncovering their application potential and developing new therapeutic approaches.…”

“…Unlike the well-known PTI (pattern-associated triggered immunity) and ETI (effector-associated triggered immunity) immune responses in plants, the broad-spectrum antimicrobial activity of BAMPs is largely due to targeting lipid structures of microbial cell membranes, thus disrupting membrane structure [ 3 , 4 ] and leading to content leakage and cell death through a combination of membrane lysis and cytotoxicity [ 5 , 6 ]. However, more complex mechanisms also exist, including interaction with specific lipids, cell cycle arrest, reactive oxygen species (ROS) production, programmed cell death, autophagy, cell signaling, and immune response [ 7 , 8 ]. BAMPs are thus responsible for durable resistance in plants.…”

Antifungal Activity of ToAP2D Peptide Against Sporothrix globosa

“…Sporothrix globosa is the predominant etiologic agent that brings about sporotrichosis in East Asia, notably in northeast China ( Yao et al, 2020 ). An epidemiologic study found that approximately 1.6 million people die from fungal infections in the world each year ( Struyfs et al, 2021a ), and a global increase in sporotrichosis incidence occurs every year, especially in the tropical and subtropical regions ( Chakrabarti et al, 2015 ). Current therapies to treat sporotrichosis are very limited, which mainly include antifungal drugs, photodynamic therapy, thermotherapy, cryotherapy, and surgery, and the effects are still far from satisfactory ( Honse et al, 2010 ; MF Matos et al, 2020 ; Soeiro Sampaio et al, 2020 ).…”

“…The plasma membrane disruption pathway indicates that the positively charged antimicrobial peptides bind to the negatively charged membrane of the pathogens, destroying its integrity, leaking contents, and causing death ( Guilhelmelli et al, 2013 ; Deslouches and Di, 2017 ; Mwangi et al, 2019 ). In addition, non-membranolytic cytotoxicity is also involved in antimicrobial activity, such as genetic material damage, immune regulation, and apoptosis ( Wassing et al, 2015 ; Struyfs et al, 2021b ). Unlike traditional antibiotics, antimicrobial peptides have many advantages such as quick killing effect and low tendency to induce resistance ( Guilhelmelli et al, 2016 ; Xu et al, 2020 ; Jayawant et al, 2021 ).…”