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Anti-Candida activity of 1-18 fragment of the frog skin peptide esculentin-1b.
No full textCandida albicans represents one of the most prevalent species causing life-threatening fungal infections. Current treatments to defeat them have become largely ineffective, due to their toxic side effects and the emergence of resistant strains. Antimicrobial peptides (AMPs) are fascinating molecules with a potential role as novel anti-infective agents. However, only a few studies have been performed on their efficacy towards the most virulent hyphal phenotype of this pathogen. The purpose of this work is to evaluate the anti-Candida activity of the N-terminal 1-18 fragment of the frog skin AMP esculentin-1b, Esc(1-18). Our results demonstrate that Esc(1-18) causes a rapid reduction in the number of viable yeast cells and killing of the hyphal population. Esc(1-18) revealed a membrane perturbing effect which is likely the basis of its mode of action. To the best of our knowledge, this is the first report showing the ability of a frog skin AMP to kill both growing stages of Candida and to inhibit transition of these fungal cells from the roundish yeast shape to the more dangerous hyphal form
Effects of aib residues insertion on the structural–functional properties of the frog skin-derived peptide esculentin-1a(1–21)NH2
No full textAntimicrobial peptides (AMPs) play a key role in the defence mechanism of living organisms against microbial pathogens, displaying both bactericidal and immunomodulatory properties. They are considered as a promising alternative to the conventional antibiotics towards which bacteria are becoming highly resistant. Recently, a derivative of the frog skin AMP esculentin-1a, esculentin-1a(1-21)NH2 [Esc(1-21)], showed a strong and fast membranolytic activity against Gram-negative bacteria but with a lower efficacy against Gram-positive ones. Here, with the aim to increase the α-helicity of Esc(1-21) and the expected potency against Gram-positive bacteria, we designed an analog bearing three α-aminoisobutyric acid (Aib) residues at positions 1, 10, and 18 of its primary structure. We demonstrated that the incorporation of Aib residues: (1) promoted the α-helix conformation of Esc(1-21), as confirmed by circular dichroism and two-dimensional nuclear magnetic resonance spectroscopies; (2) was sufficient to make this analog more active than the parent peptide against several Gram-positive bacterial strains without affecting its activity against Gram-negative bacteria; and (3) resulted to be devoid of toxic effect toward epithelial cells at the active antimicrobial concentrations. These results suggest that replacement of L-amino acids with Aib residues has beneficial effects on the structure and properties of the membrane-active peptide Esc(1-21), making it a better candidate for the design and development of selective drugs against Gram-positive bacteria
Naturally occurring peptides from Rana temporaria: antimicrobial properties and more
No full textThe extensive search for alternative therapeutics against microbial pathogens has led to the discovery of cationic peptides as new anti-infectives with a novel mode of action. Particular interest has been devoted to small linear peptides that can be efficiently made by chemical synthesis at competitive costs. The most promising originate from a large family of short, naturally occurring peptides found in the skin of amphibia of Rana genus, i.e. the temporins. This review is mainly focused on the recent structure-function studies of the earliest known temporin isoforms (TA, TB and TL) and their potential clinical role as novel antimicrobial agents. The development of novel antibiotics is an urgent public health concern due to the increased resistance of microorganisms to conventional antibiotics, particularly in the hospital setting
Temporins A and B stimulate migration of HaCaT keratinocytes and kill intracellular Staphylococcus aureus.
No full textThe growing number of microbial pathogens resistant to available antibiotics is a serious life-threat. Among them, is the bacterium Staphylococcus aureus which colonizes keratinocytes, the most abundant cell type in the epidermis. Its intracellular accumulation complicates treatments against resulting infections, mainly due to the limited diffusion of conventional drugs into the cells. Temporins A (Ta) and B (Tb) are short-sized frog skin antimicrobial peptides (AMPs). Despite extensive studies regarding their antimicrobial activity, very little is known about their activity on infected cells or involvement in various immunomodulatory functions. Here we show that Tb kills both ATCC-derived and multi-drug resistant clinical isolates of S. aureus within infected HaCaT keratinocytes (80% and 40% bacterial mortality, respectively) at a non-toxic concentration i.e. 16 μM, whereas a weaker effect is displayed by Ta. Furthermore, the peptides prevent killing of keratinocytes by the invading bacteria. Further studies revealed that both temporins promote wound healing in a monolayer of HaCaT cells with a front speed migration of 19 μm/h and 12 μm/h for Ta and Tb, respectively. Migration is inhibited by mitomycin C and involves the EGFR signaling pathway. Finally, confocal fluorescence microscopy indicated that the peptides diffuse into the cells. By combining antibacterial and wound healing activities, Ta and Tb may act as multifunctional mediators of innate immunity in humans. Particularly, their non-endogenous origin may reduce microbial resistance to them as well as the risk of autoimmune diseases in mammals
Esculentin-1a(1-21)NH2 and its diastereomer: antibacterial and immunomodulating activities
No full textMicrobial resistance to conventional antibiotics has become a major challenge. In this context, naturally-occurring antimicrobial peptides (AMPs) hold promise for the development of new drugsagainst microbial infections, including those caused by the bacterium Pseudomonas aeruginosa in the lungs of cystic fibrosis (CF) sufferers. Here we report on the in vitro activities of the frog-skin derived AMP Esculentin-1a(1-21)NH2 [Esc(1-21)], and its diastereomer Esc(1-21)-1c, containing two D-amino acids, on both macrophages and bronchial cells, which express either the functional or the ΔF508 mutant of the CF transmembrane conductance regulator (1). We found that the diastereomer is significantly less toxic; has significantly higher efficacy in killing intracellular Pseudomonas; has a higher activity in promoting migration of bronchial cells; disaggregates and detoxifies the bacterial lipopolysaccharide. These results support further studies towards the development of the Esc(1-21)-1c for local treatment of P. aeruginosainduced lung infections. This work was funded by Italian Cystic Fibrosis Research Foundation (FFC #11/2014)
The Antimicrobial Peptide Esculentin-1a(1-21)NH2: A Novel Promoter of Human Skin Wound Healing?
No full textAntimicrobial peptides (AMPs) are produced by all living organisms as a first line defense against invading microorganisms. In Amphibia, they are mainly present in the skin to form a protective chemical barrier between tissues and external environment. Esculentin-1a(1-21)NH2 [Esc(1-21)] is an amphibian skin-derived AMP with a broad spectrum of activity [1]. Unlike the human skin AMP LL-37, Esc(1-21) preserves its antimicrobial activity in biological fluids and is significantly less toxic at high concentrations. By using an in vitro modified scratch assay employing special cell-culture inserts, we found that Esc(1-21) significantly stimulates migration, but not proliferation, of immortalized human keratinocytes (HaCaT cells), more efficiently than LL-37. Importantly, this activity is preserved also on primary human epidermal keratinocytes [2]. Moreover, as previously shown for LL-37, we demonstrated that the Esc(1-21)-induced cell migration involves the activation of the epidermal growth factor receptor and STAT3 protein. Typical morphological changes associated with a migratory phenotype were detected in HaCaT cells upon treatment with Esc(1-21) [2]. These results focus on the wound healing-modulatory properties of Esc(1-21) and suggest it as a novel candidate promoter of skin re-epithelialisation, especially in the management of chronic human skin ulcers
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Anti-Candida activity of 1-18 fragment of the frog skin peptide esculentin-1b: in vitro and in vivo studies in a Caenorhabditis elegans infection model
No full textCandida albicans represents one of the most prevalent species causing life-threatening fungal infections. Current treatments to defeat Candida albicans have become quite difficult, due to their toxic side effects and the emergence of resistant strains. Antimicrobial peptides (AMPs) are fascinating molecules with a potential role as novel anti-infective agents. However, only a few studies have been performed on their efficacy towards the most virulent hyphal phenotype of this pathogen. The purpose of this work is to evaluate the anti-Candida activity of the N-terminal 1-18 fragment of the frog skin AMP esculentin-1b, Esc(1-18), under both in vitro and in vivo conditions using Caenorhabditis elegans as a simple host model for microbial infections. Our results demonstrate that Esc(1-18) caused a rapid reduction in the number of viable yeast cells and killing of the hyphal population. Esc(1-18) revealed a membrane perturbing effect which is likely the basis of its mode of action. To the best of our knowledge, this is the first report showing the ability of a frog skin AMP-derived peptide (1) to kill both growing stages of Candida; (2) to promote survival of Candida-infected living organisms and (3) to inhibit transition of these fungal cells from the roundish yeast shape to the more dangerous hyphal form at sub-inhibitory concentrations
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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