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|Autori: ||Oro, Debora|
|Supervisore afferente all'Università: ||SKERLAVAJ, BARBARA|
|Centro di ricerca: ||DIPARTIMENTO SCIENZE MEDICHE E BIOLOGICHE - DSMB|
|Titolo: ||Antimicrobial peptides for the prevention of biomedica device-related infections|
|Abstract (in inglese): ||Among health-care associated infections (HCAIs), foreign-body related infections (FBRIs) represent a clinically relevant challenge. The increasing use of implanted medical devices poses the need for materials effective in preventing such type of infections. Indeed, among the causative pathogens, multidrug resistant (MDR) strains, often forming biofilms on implant surfaces, are frequent.
Antimicrobial peptides (AMPs) are naturally occurring molecules of the innate immunity that are receiving increasing attention as potential novel anti-infective agents. This is due to their potent and broad-spectrum antimicrobial activity also including MDR strains and biofilm, their scarce propensity to select resistant mutants, and their immunomodulatory properties.
In the present thesis, the potential of five cationic α-helical AMPs as possible candidates for the manufacturing of anti-infective biomaterials was explored. The peptides under study included two mammalian cathelicidins, i.e., BMAP27 and BMAP28 (26 and 27 amino acid residues, respectively), their (1-18) N-terminal fragments (18 residues), and the in silico designed P19(9/G7) (19 residues). The in vitro antimicrobial and antibiofilm activity against S. aureus and S. epidermidis reference strains and efficacy against 24 isolates from orthopaedic infections including Staphylococcus, Streptococcus and Enterococcus spp were tested. The effects of these peptides on the viability and differentiation of osteoblast cells have also been assessed. The three shorter peptides, which displayed good antimicrobial activity and were not toxic towards eukaryotic cells, underwent further characterization in conditions mimicking the orthopaedic pathophysiological environment, i.e. in the presence of serum, hyaluronic acid and synovial fluid. Under these conditions, the peptides demonstrated overall good antimicrobial efficacy and were safe for host cells at microbicidal concentrations. They were however differently affected by the presence of human serum. The peptide BMAP27(1-18) that best retained activity in most conditions was biotinylated at the N-terminus and immobilized onto streptavidin coated resin beads. The immobilized peptide proved active against S. aureus and S. epidermidis reference strains and safe to eukaryotic cells. As a preliminary approach to elucidate the mechanism of action of the immobilized peptide, a labelled analogue of BMAP27(1-18), obtained by substitution of its four phenylalanine residues with cyano-phenylalanines, was immobilized onto the resin beads through the N- or, alternatively, through the C-terminus. Interestingly, the antimicrobial activity was retained in both cases, though to a slightly different extent.
These results encourage further studies for the development of BMAP27(1-18) as a possible peptide candidate for the functionalization of a clinically-usable biomaterial, for the prevention of biomedical-device related infections|
|Parole chiave: ||Antimicrobial peptides; Cathelicidins; Biomedical device-related infections; Immobilization; Solid support; Physiopatological conditions|
|MIUR : ||Settore BIO/10 - Biochimica|
|Corso di dottorato: ||Dottorato di ricerca in Scienze biomediche e biotecnologiche|
|Ciclo di dottorato: ||28|
|Università di conseguimento titolo: ||Università degli Studi di Udine|
|Luogo di discussione: ||Udine|
|Citazione: ||Oro, D. Antimicrobial peptides for the prevention of biomedica device-related infections. (Doctoral Thesis, Università degli Studi di Udine, 2016).|
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