Antimicrobial Peptide from the Wild Bee Hylaeus signatus Venom and Its Analogues: Structure-Activity Study and Synergistic Effect with Antibiotics.
- Resource Type
- Academic Journal
- Authors
- Nešuta O; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic.; Faculty of Food and Biochemical Technology, University of Chemistry and Technology Prague , Technická 5, 166 28 Prague 6, Czech Republic.; Hexnerová R; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic.; Buděšínský M; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic.; Slaninová J; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic.; Bednárová L; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic.; Hadravová R; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic.; Straka J; Department of Zoology, Faculty of Science, Charles University in Prague , Viničná 7, 12843 Prague 2, Czech Republic.; Veverka V; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic.; Čeřovský V; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic.
- Source
- Publisher: American Society of Pharmacognosy Country of Publication: United States NLM ID: 7906882 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-6025 (Electronic) Linking ISSN: 01633864 NLM ISO Abbreviation: J Nat Prod Subsets: MEDLINE
- Subject
- Language
- English
Venoms of hymenopteran insects have attracted considerable interest as a source of cationic antimicrobial peptides (AMPs). In the venom of the solitary bee Hylaeus signatus (Hymenoptera: Colletidae), we identified a new hexadecapeptide of sequence Gly-Ile-Met-Ser-Ser-Leu-Met-Lys-Lys-Leu-Ala-Ala-His-Ile-Ala-Lys-NH2. Named HYL, it belongs to the category of α-helical amphipathic AMPs. HYL exhibited weak antimicrobial activity against several strains of pathogenic bacteria and moderate activity against Candida albicans, but its hemolytic activity against human red blood cells was low. We prepared a set of HYL analogues to evaluate the effects of structural modifications on its biological activity and to increase its potency against pathogenic bacteria. This produced several analogues exhibiting significantly greater activity compared to HYL against strains of both Staphylococcus aureus and Pseudomonas aeruginosa even as their hemolytic activity remained low. Studying synergism of HYL peptides and conventional antibiotics showed the peptides act synergistically and preferentially in combination with rifampicin. Fluorescent dye propidium iodide uptake showed the tested peptides were able to facilitate entrance of antibiotics into the cytoplasm by permeabilization of the outer and inner bacterial cell membrane of P. aeruginosa. Transmission electron microscopy revealed that treatment of P. aeruginosa with one of the HYL analogues caused total disintegration of bacterial cells. NMR spectroscopy was used to elucidate the structure-activity relationship for the effect of amino acid residue substitution in HYL.