The antifungal effect of peptides from hymenoptera venom and their analogs

Abstract

As the occurrence of Candida species infections increases, so does resistance against commonly-used antifungal agents. It is therefore necessary to look for new antifungal drugs. This study investigated the antifungal activity of recently isolated, synthesized and characterized antimicrobial α-helical amphipathic peptides (12–18 amino acids long) from the venom of hymenoptera (melectin, lasioglossins I, II, and III, halictines I and II) as well as a whole series of synthetic analogs. The minimal inhibitory concentrations (MICs) against different Candida species (C. albicans, C. krusei, C. glabrata, C. tropicalis and C. parapsilosis) of the natural peptides amounted to 4–20 µM (7–40 mg/l). The most active were the synthetic analog all-D-lasioglossin III and lasioglossin III analog KNWKK-Aib-LGK-Aib-IK-Aib-VK-NH2. As shown using a) colony forming unit determination on agar plates, b) the efflux of the dye from rhodamine 6B-loaded cells, c) propidium iodide and DAPI staining, and d) fluorescently labeled antimicrobial peptide (5(6)-carboxyfluorescein lasioglossin-III), the killing of fungi by the peptides studied occurs within minutes and might be accompanied by a disturbance of all membrane barriers. The peptides represent a promising lead for the development of new, effective antifungal drugs.

High-throughput fluorescence screening assay for the identification and comparison of antimicrobial peptides’ activity on various yeast species

“…Over the last twenty years, the incidence of infections caused by non-albicans Candida species has risen, in particular C. glabrata has become a problem due to its intrinsic and acquired resistance to commonly used antifungal drugs (Diekema et al, 2012;Pfaller and Diekema, 2007). Lasioglossin LL-III was isolated from the venom of the eusocial bee C. albicans (Slaninová et al, 2011). In our tests with LL-III (Fig.…”

“…The peptides isolated from the venom of bees and their synthetic analogs (Čeřovský et al, 2009;Monincová et al, 2014;Slaninová et al 2011) were kindly provided by Dr. Václav…”

“…LL-III/12 is the synthetic all-D analog of LL-III (Slaninová et al, 2011). MAC-1/31 has the highest therapeutic potential from the synthesized analogs of macropin MAC-1 due to its very low haemolytic activity (LC50 > 800 μM) and sufficient antimicrobial activity against bacteria (MIC ≤ 10 μM) (Monincová et al, 2014).…”

Lasioglossins LLIII affect the morphogenesis of Candida albicans and reduces the duration of experimental vaginal candidiasis in mice

“…Three structurally related lasioglossins have been identified and named lasioglossin I, II and III. They exhibit potent antimicrobial activity against both gram‐positive and gram‐negative bacteria, and marked anti‐ Candida activity . Furthermore, they exhibit only low hemolytic activity against rat erythrocytes and low induction of mast cell degranulation which are important properties because the major drawback in application of many antimicrobial peptides is their ability to lyse eukaryotic cells, commonly expressed as hemolytic activity or, for example, anaphylaxis.…”

“…Lasioglossins exhibited potent cytotoxic activity against cancer cells in vitro . Of the three primary sequences, lasioglossin III shows the best antimicrobial , antitumor and anti‐ Candida activities .…”