Properties and mechanisms of action of naturally occurring antifungal peptides

Abstract

Antimicrobial peptides are a vital component of the innate immune system of all eukaryotic organisms and many of these peptides have potent antifungal activity. They have potential application in the control of fungal pathogens that are a serious threat to both human health and food security. Development of antifungal peptides as therapeutics requires an understanding of their mechanism of action on fungal cells. To date, most research on antimicrobial peptides has focused on their activity against bacteria. Several antimicrobial peptides specifically target fungal cells and are not active against bacteria. Others with broader specificity often have different mechanisms of action against bacteria and fungi. This review focuses on the mechanism of action of naturally occurring antifungal peptides from a diverse range of sources including plants, mammals, amphibians, insects, crabs, spiders, and fungi. While antimicrobial peptides were originally proposed to act via membrane permeabilization, the mechanism of antifungal activity for these peptides is generally more complex and often involves entry of the peptide into the cell.

Mode of Action of a Designed Antimicrobial Peptide: High Potency against Cryptococcus neoformans

“…This allows entry of the peptide into the cells, where it may have secondary targets such as DNA. It has been reported that antifungal peptides of animal as well as plant origin, such as the cysteine-rich family of AMPs, have intracellular targets and usually enter inside a cell either through receptor-mediated uptake or membrane permeabilization (5). In addition, proline-rich antifungal peptides have also been reported to translocate across the fungal membrane and interact with intracellular targets (51).…”

“…Cryptococcus neoformans is a major opportunistic fungal pathogen, linked to cryptococcosis, which may cause infection in cutaneous, pulmonary regions or even in the brain meninges (4,5). Cryptococcal meningitis is a fatal disease especially seen in HIV patients, affecting >1,000,000 people annually and leading to a death toll of~70,000 worldwide (2)(3)(4).…”

“…The current therapeutics approaches mainly include the azole group of drugs (amphotericin B, 5-fluorocytosine, and echinocandins, among others). Most of these are limited by their cytotoxic effects on the host, limited efficacy, or development of resistance in the pathogen upon long-term usage (4)(5)(6)(7). In addition, sessile biofilms act as a store house for antibiotic tolerant fungal cells that can lead to persistent systemic infections (8,9).…”

“…In addition, sessile biofilms act as a store house for antibiotic tolerant fungal cells that can lead to persistent systemic infections (8,9). The lack of antifungal agents active against biofilm-forming varieties increases the urgent need for novel agents in the drug pipeline (5,10).…”

Nicotiana alata Defensin Chimeras Reveal Differences in the Mechanism of Fungal and Tumor Cell Killing and an Enhanced Antifungal Variant

“…nnate immunity peptides have evolved in plants to protect against the damaging effects of microbial pathogens, particularly fungi (1). Fungi cause both persistent annual crop losses and devastating epidemics (2) that are a serious threat to global food security (3).…”