Lasioglossins: Three Novel Antimicrobial Peptides from the Venom of the Eusocial Bee Lasioglossum laticeps (Hymenoptera: Halictidae)

Abstract

Three novel structurally related pentadecapeptides, named lasioglossins, were isolated from the venom of the eusocial bee Lasioglossum laticeps. Their primary sequences were established as H-Val-Asn-Trp-Lys-Lys-Val-Leu-Gly-Lys-Ile-Ile-Lys-Val-Ala-Lys-NH(2) (LL-I), H-Val-Asn-Trp-Lys-Lys-Ile-Leu-Gly-Lys-Ile-Ile-Lys-Val-Ala-Lys-NH(2) (LL-II) and H-Val-Asn-Trp-Lys-Lys-Ile-Leu-Gly-Lys-Ile-Ile-Lys-Val-Val-Lys-NH(2) (LL-III). These lasioglossins exhibited potent antimicrobial activity against both Gram-positive and Gram-negative bacteria, low haemolytic and mast cell degranulation activity, and a potency to kill various cancer cells in vitro. The lasioglossin CD spectra were measured in the presence of trifluoroethanol and sodium dodecyl sulfate solution and indicated a high degree of alpha-helical conformation. NMR spectroscopy, which was carried out in trifluoroethanol/water confirmed a curved alpha-helical conformation with a concave hydrophobic and convex hydrophilic side. To understand the role of this bend on biological activity, we studied lasioglossin analogues in which the Gly in the centre of the molecule was replaced by other amino acid residues (Ala, Lys, Pro). The importance of the N-terminal part of the molecule to the antimicrobial activity was revealed through truncation of five residues from both the N and C termini of the LL-III peptide. C-terminal deamidation of LL-III resulted in a drop in antimicrobial activity, but esterification of the C terminus had no effect. Molecular modelling of LL-III and the observed NOE contacts indicated the possible formation of a bifurcated H-bond between hydrogen from the Lys15 CONH peptide bond and one H of the C-terminal CONH(2) to the Ile11 oxygen atom. Such interactions cannot form with C-terminal esterification.

Isolation of biologically active peptides from the venom of Japanese carpenter bee, Xylocopa appendiculata

“…8). These studies have unveiled the distribution of amphiphilic and biologically active peptides such as melectin from Mellecta albifrons (Apoidea: Melectini) [24], codesane from Colletes daviesanus (Colletidae) [25], osmin from Osma rufa (Megachilidae) [26], lasioglossins from Lasioglossum laticeps (Halicitidae) [27], halictines from Halictus sexcinctus (Halicitidae) [28], macropin from Macropis fulvipes (Melittidae) [29] in the bee venom. It is interesting to note that the amino acid sequences of Xac-1 and Xac-2 are similar to those of melectin and osmin isolated from the long-tonged bees, but not to those of bombolitins and melittin isolated from the social bee venom, though carpenter bees, bumblebees and honeybees are closely related.…”

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

“…The lasioglossins LLIII (amino acid sequence Val‐Asn‐Trp‐Lys‐Lys‐Ile‐Leu‐Gly‐Lys‐Ile‐Ile‐Lys‐Val‐Val‐Lys; 1764 Da) and LLIII‐D (identical sequence of amino acid D‐isomers, 1764 Da) were prepared as described elsewhere . To make stock solution, the lyophilized powder was resolved in sterile apyrogenic PBS (PAA, Dartmouth, MA, USA).…”

“…Such peptides are found, for example, in the venom of stinging insects such as the hymenopterans . Lasioglossins are a recently identified group of natural antimicrobial peptides found in the venom of the wild eusocial bee, Lasioglossum laticeps . 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 .…”

“…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 .…”