Abstract

Despite their impressive diversity and already broad therapeutic applications, cone snail venoms have received less attention as a natural source in the investigation of antimicrobial peptides than other venomous animals such as scorpions, spiders, or snakes. Cone snails are among the largest genera (Conus sp.) of marine invertebrates, with more than seven hundred species described to date. These predatory mollusks use their sophisticated venom apparatus to capture prey or defend themselves. In-depth studies of these venoms have unraveled many biologically active peptides with pharmacological properties of interest in the field of pain management, the treatment of epilepsy, neurodegenerative diseases, and cardiac ischemia. Considering sequencing efficiency and affordability, cone snail venom gland transcriptome analyses could allow the discovery of new, promising antimicrobial peptides. We first present here the need for novel compounds like antimicrobial peptides as a viable alternative to conventional antibiotics. Secondly, we review the current knowledge on cone snails as a source of antimicrobial peptides. Then, we present the current state of the art in analytical methods applied to crude or milked venom followed by how antibacterial activity assay can be implemented for fostering cone snail antimicrobial peptides studies. We also propose a new innovative profile Hidden Markov model-based approach to annotate full venom gland transcriptomes and speed up the discovery of potentially active peptides from cone snails.

Highlights

  • In 1928, Alexander Fleming discovered the widely known Penicillin from a Penicillium mold, later identified as Penicillium rubens [1]

  • Similar studies found antimicrobial peptides in snakes, spiders, bees, ants, centipedes, lugworms, wasps, and cuttlefish [15,24,25,26,27,28,29,30,31,32]. To fill this gap in cone snail venom studies, we show here the need for novel compounds in the battle against antimicrobial resistance, update the knowledge on cone snails as a source of antimicrobial peptides and present the analytical methods to decipher the venom of cone snail for antimicrobial peptides

  • Cone snail venom has already been the source of approved toxin-based drugs, and these mixtures are potential reservoirs for antimicrobial peptides

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Summary

Introduction

In 1928, Alexander Fleming discovered the widely known Penicillin from a Penicillium mold, later identified as Penicillium rubens [1]. Selman Waksman isolated Streptomycin from Streptomyces griseus [2], and together with Penicillin, both these discoveries undoubtedly revolutionized modern medicine Such antibiotics were produced in large quantities during the Second World War to successfully treat infectious diseases [3]. The iconic scorpions, spiders, and snakes, and more recently lesser-known invertebrates like cone snails, have been investigated for their venom toxins. The major component of the venom gland of cone snails is made of small peptides known as conotoxins, which often have neurotoxic activities. Similar studies found antimicrobial peptides in snakes, spiders, bees, ants, centipedes, lugworms, wasps, and cuttlefish [15,24,25,26,27,28,29,30,31,32]. To fill this gap in cone snail venom studies, we show here the need for novel compounds in the battle against antimicrobial resistance, update the knowledge on cone snails as a source of antimicrobial peptides and present the analytical methods to decipher the venom of cone snail for antimicrobial peptides

Global Antimicrobial Resistance and the Need for Novel Compounds
Cone Snails Diversity
Antimicrobial Activity of Conidae’s Conopeptides
Cone Snail Venom Extraction
Next-Generation Transcriptomics Sequencing and Bioinformatics
Venom Gland Transcriptome Annotation Based on Profile Hidden Markov Models
Updated
In Silico AMPs Structure Determination
Antibacterial Activity Assays
Findings
Conclusions
Full Text
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