Structure-Activity Relationships of Insect Defensins.

Johannes Koehbach

doi:10.3389/fchem.2017.00045

Abstract

Insects make up the largest and most diverse group of organisms on earth with several million species to exist in total. Considering the sheer number of insect species and the vast variety of ways they interact with their environment through chemistry, it is clear that they have significant potential as a source of new lead molecules. They have adapted to a range of ecological habitats and exhibit a symbiotic lifestyle with various microbes such as bacteria and fungi. Accordingly, numerous antimicrobial compounds have been identified including for example defensin peptides. Insect defensins were found to have broad-spectrum activity against various gram-positive/negative bacteria as well as fungi. They exhibit a unique structural topology involving the complex arrangement of three disulfide bonds as well as an alpha helix and beta sheets, which is known as cysteine-stabilized αβ motif. Their stability and amenability to peptide engineering make them promising candidates for the development of novel antibiotics lead molecules. This review highlights the current knowledge regarding the structure-activity relationships of insect defensin peptides and provides basis for future studies focusing on the rational design of novel cysteine-rich antimicrobial peptides.

Highlights

Peptides are known to play pivotal roles in many physiological functions and besides their action as signaling molecules they are crucial for the interaction with other organisms. This includes for example antimicrobial peptides (AMP) that represent an important part of the organism’s defense machinery or peptide toxins as part of venom cocktails (Brogden et al, 2003; Favreau et al, 2006; Aili et al, 2014)
AMPs are a diverse class of naturally occurring compounds that have been identified in a variety of organisms, from invertebrates to vertebrates including humans (Shafee et al, 2017)
In particular insects are known for their immune system that has evolved a complex arrangement of constitutive and inducible AMPs that are used to defend against invading microorganisms (Kingsolver et al, 2013) and allow a symbiotic lifestyle with various microbes (Douglas, 2015)

Summary

INTRODUCTION

Peptides are known to play pivotal roles in many physiological functions and besides their action as signaling molecules they are crucial for the interaction with other organisms. With regard to the quest for novel antimicrobial agents to target multidrug resistant pathogens such insect AMPs are promising starting points for antibiotic drug development approaches (Ageitos et al, 2016; Mahlapuu et al, 2016) The variety of these peptides, both in terms of structure as well as activity reflects the unique diversity of insect species. Based on additional secondary structure elements cysteine-rich insect AMPs can be subdivided into, (i) peptides exhibiting antiparallel triple-stranded β-sheets (e.g., Alo-3; Barbault et al, 2003), (ii) peptides that form a hairpin-like β-sheet structure (e.g., thanatin; Mandard et al, 1998) and (iii) defensins, i.e., peptides with a complex arrangement of α-helixes and β-sheets stabilized by disulfide-bonds (e.g., phormicin; Cornet et al, 1995), which are focus of this review.

V II L5

CONCLUSION