1,720,977 research outputs found

    Anti-infective antibody-derived peptides active against endogenous and exogenous fungi

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    Mycoses still represent relevant opportunistic infections worldwide, although overshad-owed in recent years by other severe and more widespread infections. Moreover, deep-seated mycoses are often accompanied by unacceptably high mortality rates. Etiologic agents include endogenous components of the mycobiota, Candida and Malassezia species above all, and exogenous species, both yeasts and filamentous fungi. Old and new fungal pathogens are increasingly charac-terized by resistance to the existing antifungal agents, making imperative the search for effective and safe new therapeutics. Among the candidate molecules proposed in recent decades, synthetic peptides derived from the complementarity determining and constant regions of diverse antibodies (Abs), as well as the translated products of Ab-encoding genes, have proved of considerable interest. Their anti-infective activities, regardless of the specificity and isotype of the originating Ab, will be briefly presented and discussed in the light of their different mechanisms of action. Intriguing suggestions on the possible function of Abs after their half-life will be presented, following the recent detection, in human serum, of an antimicrobial Ab-derived peptide. Overall, Abs could represent a source of biologically active, highly flexible peptides, devoid of detectable toxicity, which can be easily synthesized and manipulated to be used, alone or in association with already available drugs, for new anti-infective strategies

    Activity of Synthetic Peptide KP and Its Derivatives against Biofilm-Producing Escherichia coli Strains Resistant to Cephalosporins

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    Bacterial resistance to β-lactam antibiotics, particularly new generation cephalosporins, is a major public health concern. In Escherichia coli, resistance to these antibiotics is mainly mediated by extended-spectrum β-lactamases (ESBL), which complicates a range of health-threatening infections. These infections may also be biofilm-related, making them more difficult to treat because of the higher tolerance to conventional antibiotics and the host immune response. In this study, we tested as potential new drug candidates against biofilm-forming ESBL-producing E. coli four antimicrobial peptides previously shown to have antifungal properties. The peptides proved to be active in vitro at micromolar concentrations against both sensitive and ESBL-producing E. coli strains, effectively killing planktonic cells and inhibiting biofilm formation. Quantitative fluorescence intensity analysis of three-dimensional reconstructed confocal laser scanning microscopy (CLSM) images of mature biofilm treated with the most active peptide showed significant eradication and a reduction in viable bacteria, while scanning electron microscopy (SEM) revealed gross morphological alterations in treated bacteria. The screening of the investigated peptides for antibacterial and antibiofilm activity led to the selection of a leading candidate to be further studied for developing new antimicrobial drugs as an alternative treatment against microbial infections, primarily associated with biofilms

    A peptide found in human serum, derived from the c-terminus of albumin, shows antifungal activity in vitro and in vivo

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    The growing problem of antimicrobial resistance highlights the need for alternative strategies to combat infections. From this perspective, there is a considerable interest in natural molecules obtained from different sources, which are shown to be active against microorganisms, either alone or in association with conventional drugs. In this paper, peptides with the same sequence of fragments, found in human serum, derived from physiological proteins, were evaluated for their antifungal activity. A 13-residue peptide, representing the 597–609 fragment within the albumin C-terminus, was proved to exert a fungicidal activity in vitro against pathogenic yeasts and a therapeutic effect in vivo in the experimental model of candidal infection in Galleria mellonella. Studies by confocal microscopy and transmission and scanning electron microscopy demonstrated that the peptide penetrates and accumulates in Candida albicans cells, causing gross morphological alterations in cellular structure. These findings add albumin to the group of proteins, which already includes hemoglobin and antibodies, that could give rise to cryptic antimicrobial fragments, and could suggest their role in anti-infective homeostasis. The study of bioactive fragments from serum proteins could open interesting perspectives for the development of new antimicrobial molecules derived by natural sources

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    Antibacterial effects of two synthetic peptides against Enterococcus faecalis biofilms: A preliminary in vitro study

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    Aim: Current endodontic techniques are unable to fully eradicate intracanal bacteria. Thus, new agents that effectively eliminate endodontic pathogens are needed. The aim of this study was to assess the antibacterial properties of two synthetic peptides, namely KP and L18R, against planktonic cells and biofilms of the endodontic pathogen Enterococcus faecalis. Methodology: KP and L18R bactericidal activity against E. faecalis ATCC 29212 was evaluated by colony forming unit assays and the half maximal effective concentration (EC50) was calculated. The effect of peptides on E. faecalis biofilm formation onto polystyrene plates was also assessed by the crystal violet assay. Confocal laser scanning microscopy (CLSM) analysis was carried out to compare the effects of KP, L18R and a Ca(OH)2 saturated solution in an in vitro model of dental infection consisting in 2-day-old E. faecalis biofilms grown on hydroxyapatite disks. Results: Both KP and L18R showed strong bactericidal activity against planktonic E. faecalis. L18R proved to be 10-folds more ef fective than KP (KP and L18R EC50 values=4.520×10-6 M and 3.624×10-7 M, respectively). Peptides inhibited E. faecalis biofilm formation in a dose-dependent manner and L18R resulted more effectivethan KP. CLSM images showed that Ca(OH)2, KP and L18R remarkably impaired E. faecal is biof i lms pre -grown on hydroxyapatite. Conclusions: KP and L18R effectively inhibited E. faecalis, both in planktonic and biofilm form. L18R demonstrated a more potent antibacterial activity than KP. These preliminary results suggest that antimicrobial peptides may represent a promising new strategy for endodontic infection control

    The Variability of the Salivary Antimicrobial Peptide Profile: Impact of Lifestyle

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    Saliva is crucial in maintaining oral health; its composition reflects the body’s physiological and diseased state. Among salivary components, antimicrobial peptides (AMPs) stand out for their broad antimicrobial activities and role in modulating the oral microbiota and innate immune response. Local and systemic diseases can affect the levels of AMPs in saliva, making them attractive biomarkers. However, the large variability in their concentrations hampers their use in diagnostics. Knowledge of the various factors influencing the profile of salivary AMPs is essential for their use as biomarkers. Here, we examine how lifestyle factors such as physical activity, dietary supplementation, tobacco smoking, and psychological stress impact salivary AMP levels. By understanding these sources of variability, we can take a step forward in using AMPs for diagnostics and prognostics and develop new tailored and preventative approaches

    Wickerhamomyces yeast killer toxins’ medical applications

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    Possible implications and applications of the yeast killer phenomenon in the fight against infectious diseases are reviewed, with particular reference to some wide-spectrum killer toxins (KTs) produced by Wickerhamomyces anomalus and other related species. A perspective on the applications of these KTs in the medical field is provided considering (1) a direct use of killer strains, in particular in the symbiotic control of arthropod-borne diseases; (2) a direct use of KTs as experimental therapeutic agents; (3) the production, through the idiotypic network, of immunological derivatives of KTs and their use as potential anti-infective therapeutics. Studies on immunological derivatives of KTs in the context of vaccine development are also described

    Activity of two antimicrobial peptides against Enterococcus faecalis in a model of biofilm-mediated endodontic infection

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    Enterococcus faecalis is a common cause of biofilm-associated opportunistic infections, which are often difficult to treat. The formation of E. faecalis biofilms on the dentinal walls of the root canal is frequently the cause of endodontic treatment failure and secondary apical periodontitis. In a preliminary work, two recognized antifungal peptides, KP and L18R, showed antibacterial activity against planktonic E. faecalis cells at micromolar concentrations. Moreover, L18R proved to reduce the biomass in the early stage of E. faecalis biofilm development on polystyrene plates, while a qualitative biofilm inhibition was demonstrated on hydroxyapatite disks by confocal laser scanning microscopy (CLSM). The aim of this study was to better characterize the effect of both peptides on E. faecalis biofilm. A reduction in metabolic activity after peptide treatment was detected by Al-amar Blue assay, while a remarkable impairment in the architecture of E. faecalis biofilms on hy-droxyapatite disks, along with a significant reduction in viable bacteria, was caused mostly by L18R, as assessed by CLSM and scanning electron microscopy. The lack of cytotoxicity of the investigated peptides against L929 murine fibroblasts was also determined. Obtained results suggest L18R as a promising candidate for the development of new strategies for endodontic infection control
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