Cesaro, Angela (2021) Development of innovative antimicrobials for cosmeceutical applications. [Tesi di dottorato]


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Item Type: Tesi di dottorato
Resource language: English
Title: Development of innovative antimicrobials for cosmeceutical applications
Cesaro, Angelaangela.cesaro@unina.it
Date: 15 April 2021
Number of Pages: 180
Institution: Università degli Studi di Napoli Federico II
Department: Biologia
Dottorato: Biotecnologie
Ciclo di dottorato: 33
Coordinatore del Corso di dottorato:
Moracci, Marcomarco.moracci@unina.it
Arciello, AngelaUNSPECIFIED
Date: 15 April 2021
Number of Pages: 180
Keywords: Antimicrobial peptide (AMPs), antibiotic resistance, skin infections, hyaluronic acid-based hydrogel
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/10 - Biochimica
Date Deposited: 21 Apr 2021 06:26
Last Modified: 07 Jun 2023 11:07
URI: http://www.fedoa.unina.it/id/eprint/14100

Collection description

As a physical and chemical barrier, the skin arrests pathogens invasion, thus preventing harmless or even potentially lethal infections. When this barrier is damaged, the spread of infections is usually treated by using traditional antibiotics, which are often ineffective on Multi-Drug resistant bacteria. Antibiotic resistance is predicted to become the leading cause of death in our society, thus justifying the search for novel antimicrobials derived from previously underexplored sources. In this context, promising molecules as the antimicrobial peptides (AMPs) represent an innovative alternative, since the evolution of resistance against these compounds generally does not occur. Encrypted peptides deriving from human proteome represent a yet unexplored source of a novel class of antibiotics. In this Research project, we report that peptides hidden within human plasma display broad-spectrum antibiotic properties. Specifically, three peptides [r(P)ApoBLPro, r(P)ApoBSPro and r(P)ApoBLAla] derived from human apolipoprotein B (residues 887-922) exhibited potent antimicrobial activity against drug-resistant Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococci both in vitro and in animal models. These peptides were found to target bacteria by depolarizing their cytoplasmic membranes and to inhibit biofilm. Importantly, the peptides were found to potentiate the activity of conventional antibiotics against bacteria and did not select for bacterial resistance even after a prolonged exposure of bacterial cells. In addition to their direct antimicrobial and antibiofilm activities, ApoB encrypted peptides displayed excellent toxicity profiles. To ensure translatability of these molecules, a retro-inverso variant [(ri)-r(P)ApoBSPro] of the lead encrypted peptide was synthesized. The peptidomimetic here engineered was found to be resistant to proteases and demonstrated to preserve the bioactivities of the parental peptides with even stronger efficacy when tested in a pre-clinical mouse model. Finally, a hyaluronic acid-based hydrogel functionalized with (ri)-r(P)ApoBSPro was designed and characterized. The hydrogel system loaded with the retro-inverso variant of ApoB encrypted peptide was found to inhibit bacterial growth, to prevent pathogens migration and to stimulate cells viability. Altogether, obtained data open new avenues for the discovery of a novel generation of antibiotics from human blood and highlight the applicability of ApoB-derived peptides in the treatment of skin infections and diseases.


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