Bioinformatics Discovery of Vertebrate Cathelicidins from the Mining of Available Genomes (original) (raw)
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Antimicrobial agents and chemotherapy, 2017
In this study, we sought to identify novel antimicrobial peptides (AMPs) in Python bivittatus through bioinformatic analyses of publicly available genome information and experimental validation. In our analysis of the python genome, we identified 29 AMP-related candidate sequences. Of these, we selected five cathelicidin-like sequences and subjected them to further in silico analyses. The results showed that these sequences likely have antimicrobial activity. The sequences were named Pb-CATH1-Pb-CATH5 according to their sequence similarity to previously reported snake cathelicidins. We predicted their molecular structure, and then chemically synthesized the mature peptide for three putative cathelicidins and subjected them to biological activity tests. Interestingly, all three peptides showed potent antimicrobial effects against Gram-negative bacteria, but very weak activity against Gram-positive bacteria. Remarkably, ΔPb-CATH4 showed potent activity against antibiotic-resistance cl...
Peptides, 2012
A remarkable and intriguing challenge for the modern medicine consists in the development of alternative therapies to avoid the problem of microbial resistance. The cationic antimicrobial peptides present a promise to be used to develop more efficient drugs applied to human health. The in silico analysis of genomic databases is a strategy utilized to predict peptides of therapeutic interest. Once the main antimicrobial peptides' physical-chemical properties are already known, the correlation of those features to search on these databases is a tool to shorten identifying new antibiotics. This study reports the identification of antimicrobial peptides by theoretical analyses by scanning the Paracoccidioides brasiliensis transcriptome and the human genome databases. The identified sequences were synthesized and investigated for hemocompatibility and also antimicrobial activity. Two peptides presented antifungal activity against Candida albicans. Furthermore, three peptides exhibited antibacterial effects against Staphylococcus aureus and Escherichia coli; finally one of them presented high potential to kill both pathogens with superior activity in comparison to chloramphenicol. None of them showed toxicity to mammalian cells. In silico structural analyses were performed in order to better understand function-structure relation, clearly demonstrating the necessity of cationic peptide surfaces and the exposition of hydrophobic amino acid residues. In summary, our results suggest that the use of computational programs in order to identify and evaluate antimicrobial peptides from genomic databases is a remarkable tool that could be used to abbreviate the search of peptides with biotechnological potential from natural resources.
PLoS ONE, 2014
Cathelicidins, a class of gene-encoded effector molecules of vertebrate innate immunity, provide a first line of defense against microbial invasions. Although cathelicidins from mammals, birds, reptiles and fishes have been extensively studied, little is known about cathelicidins from amphibians. Here we report the identification and characterization of two cathelicidins (cathelicidin-RC1 and cathelicidin-RC2) from the bullfrog Rana catesbeiana. The cDNA sequences (677 and 700 bp, respectively) encoding the two peptides were successfully cloned from the constructed lung cDNA library of R. catesbeiana. And the deduced mature peptides are composed of 28 and 33 residues, respectively. Structural analysis indicated that cathelicidin-RC1 mainly assumes an amphipathic alpha-helical conformation, while cathelicidin-RC2 could not form stable amphipathic structure. Antimicrobial and bacterial killing kinetic analysis indicated that the synthetic cathelicidin-RC1 possesses potent, broad-spectrum and rapid antimicrobial potency, while cathelicidin-RC2 exhibited very weak antimicrobial activity. Besides, the antimicrobial activity of cathelicidin-RC1 is salt-independent and highly stable. Scanning electron microscopy (SEM) analysis indicated that cathelicidin-RC1 kills microorganisms through the disruption of microbial membrane. Moreover, cathelicidin-RC1 exhibited low cytotoxic activity against mammalian normal or tumor cell lines, and low hemolytic activity against human erythrocytes. The potent, broad-spectrum and rapid antimicrobial activity combined with the salt-independence, high stability, low cytotoxic and hemolytic activities make cathelicidin-RC1 an ideal template for the development of novel peptide antibiotics.
Cathelicidins: family of antimicrobial peptides. A review
Molecular Biology Reports, 2012
Cathelicidins are small, cationic, antimicrobial peptides found in humans and other species, including farm animals (cattle, horses, pigs, sheep, goats, chickens, rabbits and in some species of fish). These proteolytically activated peptides are part of the innate immune system of many vertebrates. These peptides show a broad spectrum of antimicrobial activity against bacteria, enveloped viruses and fungi. Apart from exerting direct antimicrobial effects, cathelicidins can also trigger specific defense responses in the host. Their roles in various pathophysiological conditions have been studied in mice and humans, but there are limited information about their expression sites and activities in livestock. The aim of the present review is to summarize current information about these antimicrobial peptides in farm animals, highlighting peptide expression sites, activities, and future applications for human and veterinary medicine.
Characterization and Identification of Natural Antimicrobial Peptides on Different Organisms
International Journal of Molecular Sciences, 2020
Because of the rapid development of multidrug resistance, conventional antibiotics cannot kill pathogenic bacteria efficiently. New antibiotic treatments such as antimicrobial peptides (AMPs) can provide a possible solution to the antibiotic-resistance crisis. However, the identification of AMPs using experimental methods is expensive and time-consuming. Meanwhile, few studies use amino acid compositions (AACs) and physicochemical properties with different sequence lengths against different organisms to predict AMPs. Therefore, the major purpose of this study is to identify AMPs on seven categories of organisms, including amphibians, humans, fish, insects, plants, bacteria, and mammals. According to the one-rule attribute evaluation, the selected features were used to construct the predictive models based on the random forest algorithm. Compared to the accuracies of iAMP-2L (a web-server for identifying AMPs and their functional types), ADAM (a database of AMP), and MLAMP (a multi-l...
Journal of Biological Chemistry, 1996
Cathelicidins are a family of myeloid antimicrobial peptide precursors that have been identified in several mammalian species (Zanetti, M., Gennaro, R., and Romeo, D. (1995) FEBS Lett. 374, 1-5). Two novel bovine congeners have been deduced from cDNA. Their C-terminal sequences of 27 and 28 residues correspond to putative antimicrobial peptides with a cationic N-terminal region predicted to assume an amphipathic ␣-helical conformation followed by a hydrophobic C-terminal tail. Peptides corresponding to these sequences have been chemically synthesized and shown to exert a potent antimicrobial activity against Gram-negative and Grampositive bacteria, including methicillin-resistant Staphylococcus aureus, and fungi. Both peptides are also cytotoxic to human erythrocytes and neutrophils, although at higher than microbicidal concentrations. The target selectivity has been improved by synthesizing truncated analogues, comprising only the 18 N-terminal residues, which show a great reduction in cytotoxic, but not in antimicrobial activity. The involvement of the C-terminal hydrophobic tail in the cytotoxic activity has been further demonstrated by inducing a major loss of activity in an analogue after replacing highly hydrophobic residues with more hydrophilic ones.
A review on antimicrobial peptides databases and the computational tools
Database, 2022
Antimicrobial Peptides (AMPs) have been considered as potential alternatives for infection therapeutics since antibiotic resistance has been raised as a global problem. The AMPs are a group of natural peptides that play a crucial role in the immune system in various organisms AMPs have features such as a short length and efficiency against microbes. Importantly, they have represented low toxicity in mammals which makes them potential candidates for peptide-based drugs. Nevertheless, the discovery of AMPs is accompanied by several issues which are associated with labour-intensive and time-consuming wet-lab experiments. During the last decades, numerous studies have been conducted on the investigation of AMPs, either natural or synthetic type, and relevant data are recently available in many databases. Through the advancement of computational methods, a great number of AMP data are obtained from publicly accessible databanks, which are valuable resources for mining patterns to design ...
Phylogenetic characterization of novel cathelicidin from Indian water buffalo
2016
The bubaline cathelicidins have been an important area of research because of possibility of exploring novel antimicrobial peptides (AMPs) in the buffaloes, which are comparatively more sturdy animals and are better adapted to Indian climate as compared to the crossbred cattle. The rationale behind the current study was to in silico characterize the cloned bubaline cathelicidin3 (Cath3) peptide and to study the evolution of bubaline caths. Multiple sequence alignment of the bubaline Cath3 (from this study) and homologous peptide sequences revealed an insertion of 6 amino acids in the cathelin domain of the bubaline Cath3 peptide when compared with that of cattle. Biocomputational analyses of the Cath3 coding sequence (cds) as well as the amino acid sequences (using MEGA6 software & Datamonkey server) indicated that different types and transcript variants of cathelicidin varied considerably within the same species, indicating the role of natural selection during the evolution of cath...
Antimicrobial Activity of Cathelicidin-Derived Peptide from the Iberian Mole Talpa occidentalis
Vaccines
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 antimicro...
Amphibian cathelicidin fills the evolutionary gap of cathelicidin in vertebrate
Amino Acids, 2011
Cathelicidins comprise a family of antimicrobial peptides (AMPs) sharing a highly conserved cathelin domain, and play a central role in the innate defense against infection in most of vertebrates. But so far it has not yet been found in amphibians although a large number of other groups of AMPs have been identified. In the current work, the first amphibian cathelicidin (cathelicidin-AL) has been characterized from the frog skin of Amolops loloensis. Cathelicidin-AL (RRSRRGRGGGRRGGSGGRGGRGGG GRSGAGSSIAGVGSRGGGGGRHYA) is a cationic peptide containing 48 amino acid residues (aa) with 12 basic aa and no acidic aa. The chemical synthesized peptide efficiently killed bacteria and some fungal species including clinically isolated drug-resistance microorganisms. The cDNA encoding cathelicidin-AL precursor was cloned from the skin cDNA library of A. loloensis. As other cathelicidins, the precursor of cathelicidin-AL also contains highly conserved anionic cathelin domain of cysteine proteinase inhibitor followed by the AMP fragment at C-terminus. Phylogenetic analysis revealed that as connecting link, the amphibian cathelicidin predates reptilia but postdates fish cathelicidin. The peptide purification combined with gene cloning results confirms the presence of cathelicidin in amphibians and filled the evolutionary gap of cathelicidin in vertebrate, considering amphibians' special niche as the animals bridging the evolutionary landwater gap.