Ianniello, Flora (2017) Identification and characterization of antimicrobial agents to control bacterial infection. [Tesi di dottorato]
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| Tipologia del documento: | Tesi di dottorato | ||||
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| Lingua: | English | ||||
| Titolo: | Identification and characterization of antimicrobial agents to control bacterial infection | ||||
| Autori: |
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| Data: | 9 Aprile 2017 | ||||
| Numero di pagine: | 93 | ||||
| Istituzione: | Università degli Studi di Napoli Federico II | ||||
| Dipartimento: | Scienze Chimiche | ||||
| Dottorato: | Biotecnologie | ||||
| Ciclo di dottorato: | 29 | ||||
| Coordinatore del Corso di dottorato: |
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| Data: | 9 Aprile 2017 | ||||
| Numero di pagine: | 93 | ||||
| Parole chiave: | Antibiotic resistance, antimicrobial peptides, bacteriophages | ||||
| Settori scientifico-disciplinari del MIUR: | Area 05 - Scienze biologiche > BIO/19 - Microbiologia generale Area 06 - Scienze mediche > MED/07 - Microbiologia e microbiologia clinica |
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| Depositato il: | 07 Mar 2018 09:20 | ||||
| Ultima modifica: | 12 Mag 2018 01:00 | ||||
| URI: | http://www.fedoa.unina.it/id/eprint/11933 | ||||
| DOI: | 10.6093/UNINA/FEDOA/11933 |
Abstract
The inappropriate and excessive use of antibiotics in medicine and agriculture led to the development of antibiotic resistant bacteria as shown by the data presented by the ECDC (European Centre for Prevention and Disease Control) and the HI (Health Institute). The development of new therapeutic agents is necessary to cope with this emergency. The characteristics demanded to new antibacterial drugs are greater selectivity and a different mechanism of action compared to traditional drugs in use. The peculiar properties of peptides and phages make their use attractive to counter the problem of antibiotic resistance. The CAMPs are widely distributed in nature and differ in terms of length, primary and secondary structures, but they all have the characteristics of being cationic and amphipathic. The CAMPs have as " target” the bacterial cell membrane. This structure is highly conserved among bacteria and its reorganization would be highly expensive and difficult to realize. Bacteriophages are viruses that specifically infect bacterial cells. They do not harm the natural flora of the human host when used as antimicrobial agents. In this study, we used the antimicrobial peptide PAP3 (A3 isoform of human pepsinogen) and the phage 1 (isolated by Salmonella rissen). PAP3 displays a strong antimicrobial activity against several bacterial species (at the concentration of 220 μg/mL inhibits 90%-100% of bacteria). Unfortunately, PAP3 is toxic for eukaryotic cells, even at low concentration and for this reason it has not been studied further. On the contrary, the phage 1, - isolated and characterized in the course of this study - is a good antimicrobial agent. To the same extent of all the other phages, phage 1 is species-specific, is not toxic to eukaryotic cells and one single dose of phage is sufficient to control bacterial infection. To date, no phage preparation for intracellular pathogens is available. In this study – for the first time – it was tested the use of hydroxyapatite as a vehicle to carry phage 1 inside the eukaryotic cell. It was shown that hydroxyapatite carries the phage inside eukaryotic cells and does it without damaging the cells. The hydroxyapatite, Ca5 (PO4)3 (OH), is a rare mineral of the apatite group. It has the shape of a hexagonal prism and serves as protective scaffold and as carrier of bioactive molecules. Our results show that the complex (phage-hydroxyapatite) is more stable than phage alone, is active at pH 2 and is a good agent to reduce bacterial contamination in the food. Based on our results, we believe that the use of bacteriophages complexed with hydroxyapatite represents a promising biotechnological approach to treat /to prevent bacterial infections in several areas.
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