Combined Proteotranscriptomic-Based Strategy to Discover Novel Antimicrobial Peptides from Cone Snails

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.

Identification of distinct characteristics of antibiofilm peptides and prospection of diverse sources for efficacious sequences

“…Ponericins, peptides from the Ponerine ant, have structural similarity with well-known antimicrobial and antibiofilm peptide cecropins [43]. While no known antimicrobial activity has been listed for the histamine releasing peptide from the oriental hornet, studies are ongoing for alpha-conotoxin obtained from cone snails, mainly used in pain management, to establish its antimicrobial activity [44]. An analog, ω -conotoxin MVIIA shows the peptide is effective against Candida kefyr and Candida tropicalis with moderate MIC values between 28–40 μM but it was not effective against any bacterial assay up to 500 μM [45].…”

Identification of Distinct Characteristics of Antibiofilm Peptides and Prospection of Diverse Sources for Efficacious Sequences

“…Ponericins, peptides from the Ponerine ant, have structural similarity with well-known antimicrobial and antibiofilm peptide cecropins (Orivel et al, 2001). While no known antimicrobial activity has been listed for the histamine releasing peptide from the oriental hornet, studies are ongoing for alpha-conotoxin obtained from cone snails, mainly used in pain management, to establish its antimicrobial activity (Ebou et al, 2021). An analog, ω-conotoxin MVIIA shows the peptide is effective against Candida kefyr and Candida tropicalis with moderate MIC values between 28 and 40 µM but it was not effective against any bacterial assay up to 500 µM (Hemu and Tam, 2017).…”

High-throughput prediction and characterization of antimicrobial peptides from multi-omics datasets of Chinese tubular cone snail (Conus betulinus)

“…With the wide application of AMPs in immunity and disease resistance, it is necessary to identify AMPs quickly and efficiently. High-throughput prediction of AMPs from genome and transcriptome datasets is one of the practical effective methods for discovery of novel AMPs sequences (Amaral et al, 2012;Houyvet et al, 2018;Ebou et al, 2021). By employing multi-omics analysis, we were able to obtain sequences of those potential AMP-derived genes, and further to illustrate their expression patterns in different individuals and various tissues of the same Conus species.…”

“…The complex multi-component venom contains various bioactive peptides including AMPs, which have been identified in diverse toxic animals such as spiders, snakes, scorpions and bees for promising therapeutic drug developments (de Barros et al, 2019;Tang et al, 2020;Khalil et al, 2021;Tawfik et al, 2021). AMPs in cone snails seem to be less attentional (Yang et al, 2001;Periyasamy et al, 2012;De León-Nava et al, 2016;Bernaĺdez-Sarabia et al, 2019;Younis et al, 2019;Ebou et al, 2021) compared to other animals. A previous study reported that a O1-superfamily conotoxin extracted from Californian cone (Californiconus californicus) venom can inhibit the growth of bacteria Mycobacterium tuberculosis (Bernaĺdez-Sarabia et al, 2019).…”

“…Another type of conotoxin, namely wconotoxin MVIIA with identification from several cone snails as cyclic analogs, has shown antimicrobial activity against various bacteria (Yang et al, 2001;Hemu and Tam, 2017). With the explosion of multi-omics data, a recent review reported a proteotranscriptomic-based strategy to identify AMPs from cone snails (Ebou et al, 2021).…”