Antifungal peptide 1

This study investigatedthe mechanism of epinecidin-1 against Botrytis cinerea, in vitro, and its effectiveness at inhibiting gray mold on postharvest peach fruit. We found that in vitro, epinecidin-1 had significantly greater antifungal activity against B. cinerea than either clavanin-A or mytimycin, two other marine derived antimicrobial peptides that we tested. Its antifungal activity was heat-resistant (15 min at 40-100 °C) and tolerant to lower concentrations of cations (<100 mM Na+, K+; <10 mM Ca2+). Epinecidin-1 interacted directly with B. cinerea genomic DNA, and that in mycelia, epinecidin-1 exposure induced accumulation of intracellular ROS and increased the permeability of cell membranes resulting in leakage of nucleic acids and aberrant cell morphology. Meanwhile, 200 μM of epinecidin-1 had a significant inhibitory effect on gray mold injected into peach fruit. These results suggested that epinecidin-1 showed promise as a potential method for controlling postharvest gray mold in peaches.

Invasive fungal diseases primarily occur in immunocompromised patients. Immunosuppression has become more prevalent due to novel treatments, and this has led to a rise in the incidence of invasive fungal diseases. The antifungal armamentarium has long been insufficient and has taken quite some time to become diverse. Antifungal spectrum, tolerability, and toxicity are critical issues. Amphotericin B and its lipid formulations still have the widest spectrum, but, in spite of the better tolerance of the lipid formulations, toxicity remains a drawback, mostly with regard to renal function. Azoles constitute a heterogeneous antifungal class, in which newer molecules have an improved spectrum of activity. The main concern for the clinician when using azoles relates to the management of their many potential drug-drug interactions in an often fragile patient population. Echinocandins are better tolerated but possess a narrower antifungal spectrum and lack an oral route of administration. Still, their fungicidal activity makes them a weapon of first choice against Candida species. For certain uncommon fungal infections, antifungals such as flucytosine and terbinafine can also be useful. This article will give an overview of the mechanisms of action of currently used antifungals, as well as their spectrum of activity, clinically relevant pharmacological features, drug-drug interactions, and frequent side effects, all of which should drive the clinician's choice of agent when managing invasive fungal infections.

The development of novel antifungal agents with high efficacy, low drug tolerance and few side effects is urgent. MSI-1 (GIWKFLKKAKKFWK-NH2), a cationic antimicrobial peptide, may be an attractive antifungal agent because of its structural characteristics, perfect stability against pH and high-temperature/salt, low toxicity towards mammalian cells and low potential for emergence of drug tolerance. In this study, the antifungal activity of MSI-1 in vitro and in a murine model of cryptococcal meningoencephalitis was evaluated. Zeta potential assay, flow cytometry, fluorescence microscope, transmission electron microscopy and microscale thermophoresis were performed to clarify the mechanisms underlying MSI-1 against C. neoformans. The results showed that MSI-1 exerted effective anti-cryptococcal activity in vitro, with MICs of 8-16 μg/mL and MFCs of 8-32 μg/mL, and in a C neoformans-infected mouse model, with significantly improved animal survival, decreased production of pro-inflammatory cytokines and alleviated lung injury, because the potent and rapid fungicidal activity of MSI-1 could effectively eliminate fungal counts in mouse organs. We confirmed that the positively charged peptide bound to C. neoformans by electrostatic attraction after interacting with glucuronoxylomannan (the primary component of C. neoformans capsule). Subsequently, MSI-1 increased the membrane fluidity of fungal cells and the cell membrane permeability, causing destabilized membrane integrity and leading to the final death of fungi. Collectively, MSI-1 possessed potent anti-cryptococcal activity via its notable membrane disruption effect and may be a potential candidate for use in antifungal infection induced by C. neoformans, especially azole-resistant cryptococcus.