Abstract

Butterflies represent one of the largest animal groups on Earth, yet antimicrobial peptides (AMPs) of this group are less studied in comparison with their moth counterparts. This study employed an integrated bioinformatics approach to survey natural AMPs from publicly available genomic datasets. Numerous AMPs, including cecropins, defensins, and moricins, were identified and subsequently used as templates for the design of a series of synthetic AMPs that mimicked the naturally occurring sequences. Despite differing biological effects among the various sequences, the synthetic AMPs exhibited potent antibacterial and antifungal activities in vitro and in vivo, without inducing hemolysis, which implied their therapeutic potential in infectious diseases. Electron and confocal fluorescence microscopies revealed that the AMPs induced distinct morphological and biophysical changes on microbial cell membranes and nuclei, suggesting that the antimicrobial effects were related to a mechanism of membrane penetration and nucleic acid binding by the peptides. In conclusion, this study not only offers insights into butterfly AMPs but also provides a practical strategy for high-throughput natural AMP discoveries that will have implications for future research in this area.

Highlights

  • Infectious diseases were a major problem in human history until the development of various efficacious antibiotics that target the causative microorganisms

  • Available genomic sequencing datasets from 32 Papilionoidea species of six families deposited in the Gene Expression Omnibus (GEO) database up to January 2019 were downloaded for analyses

  • This set of peptide sequences was merged with available sequences obtained by database query and literature research

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Summary

Introduction

Infectious diseases were a major problem in human history until the development of various efficacious antibiotics that target the causative microorganisms. AMPs have received considerable attention as a promising group of molecules due to their unique mechanism of rapid physical disruption of microbial membranes, this dogma is being challenged, as alternative targets have been reported (Manniello et al, 2021). This mechanism is preferable for suppression of the deteriorating resistance problem because microbes are eliminated regardless of antibiotic sensitivity or resistance, and AMPs are not prone to inducing resistant mutants (Zharkova et al, 2019). Other desirable properties such as broad-spectrum activity and low host toxicity make AMPs appropriate alternatives to antibiotics (Hazam et al, 2019)

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