Insects make up the largest and most diverse group of organisms on earth with estimated numbers of around 4,000,000 species to exist in total. Their immune system has evolved a complex arrangement of constitutive and inducible antimicrobial peptides (AMP) that are used to defend against invading microorganisms or allow a symbiotic lifestyle with a variety of microbes including bacteria and fungi. Several insect AMPs were found to exhibit broad-spectrum activity against various human pathogens and thus they are considered as promising candidates for novel antibiotic drug development.
In our current work we focus on the class of insect defensins. These peptides exhibit a well-defined structure consisting of a complex arrangement of α-helixes and β-sheets that are stabilized by three intramolecular disulfide-bonds. Together with a range of reported activities they represent ideal templates for structure-activity studies.
Using a thorough in silico mining approach we analysed >140 insect species and were able to identify a series of novel cysteine-rich defensin and defensin-like peptides. Interestingly, we show their presence or absence to be confined within individual species and orders. Subsequently, solid-phase peptide synthesis is applied to generate sufficient material for both NMR structural studies as well as bioactivity testing against a range of human pathogens.
This work not only identifies novel defensin peptides and investigates their potential as novel antibiotic lead molecules, but also provides insights into the role of defensin peptides in insect ecology.