Antimicrobial Activity of Cathelicidin-Derived Peptide from the Iberian Mole Talpa occidentalis

Abstract

The immune systems of all vertebrates contain cathelicidins, a family of antimicrobial peptides. Cathelicidins are a type of innate immune effector that have a number of biological functions, including a well-known direct antibacterial action and immunomodulatory function. In search of new templates for antimicrobial peptide discovery, we have identified and characterized the cathelicidin of the small mammal Talpa occidentalis. We describe the heterogeneity of cathelicidin in the order Eulipotyphla in relation to the Iberian mole and predict its antibacterial activity using bioinformatics tools. In an effort to correlate these findings, we derived the putative active peptide and performed in vitro hemolysis and antimicrobial activity assays, confirming that Iberian mole cathelicidins are antimicrobial. Our results showed that the Iberian mole putative peptide, named To-KL37 (KLFGKVGNLLQKGWQKIKNIGRRIKDFFRNIRPMQEA) has antibacterial and antifungal activity. Understanding the antimicrobial defense of insectivores may help scientists prevent the spread of pathogens to humans. We hope that this study can also provide new, effective antibacterial peptides for future drug development.

Translational aspect in peptide drug discovery and development: An emerging therapeutic candidate

“…Since the active mature cathelicidins do not share sequence similarities, these peptides are named after the conserved cathelin-like domain in the propeptide, which is the common denominator of this peptide family 120 and its conserved sequence is useful for the discovery of cathelicins in other vertebrates. 121,122 The broad spectrum of natural antimicrobial peptide sequences and structures enables the discovery and development of innovative therapeutic peptide analogs or peptidomimetics. 123,124 The development of new therapeutic candidates based on the HDPs involves various techniques such as substitution of single amino acids, use of internal parts of the HDPs to produce smaller peptides, and in silico methods to anticipate novel synthetic peptides based on structure-function relationships.…”

“…Once the peptide is released, the pro‐cathelin‐like domain is extensively cleaved by serine proteases. Since the active mature cathelicidins do not share sequence similarities, these peptides are named after the conserved cathelin‐like domain in the propeptide, which is the common denominator of this peptide family 120 and its conserved sequence is useful for the discovery of cathelicins in other vertebrates 121,122 …”

The Role of Reactive Species on Innate Immunity

“…Antimicrobial peptides AMPs are an important component of the innate immune system in all organisms, including plants, animals, and humans, providing a rapid and non-specific response to pathogens [ 175 ]. Cathelicidins and defensins are a family of antimicrobial peptides that show a wide spectrum of antimicrobial activity against bacteria, enveloped viruses, and fungi [ 176 ]. Many antimicrobial peptides are stored in the lysosomes of macrophages and polymorphonuclear leukocytes, where they are part of the oxygen-independent activity against pathogens [ 177 , 178 ].…”

Cathelicidin-HG Alleviates Sepsis-Induced Platelet Dysfunction by Inhibiting GPVI-Mediated Platelet Activation

“…Naturally occurring peptides have shown enormous potential as therapeutic agents [ 6 – 8 ]. Among them, the Cathelicidins, a class of natural antimicrobial peptides widely present in vertebrates, have been shown to possess multiple biological activities [ 9 , 10 ]. Amphibians are one of the important sources of Cathelicidins, and many Cathelicidins have been identified in this group [ 11 – 15 ].…”