VOLLARO, ADRIANA
(2017)
Antimicrobial Activity of Natural and Synthetic Compounds Against Candida spp., Gram-Positive and Gram-Negative Bacteria.
[Tesi di dottorato]
| Tipologia del documento: |
Tesi di dottorato
|
| Lingua: |
English |
| Titolo: |
Antimicrobial Activity of Natural and Synthetic Compounds Against Candida spp., Gram-Positive and Gram-Negative Bacteria |
| Autori: |
| Autore | Email |
|---|
| VOLLARO, ADRIANA | vollaroadriana@libero.it |
|
| Data: |
11 Dicembre 2017 |
| Numero di pagine: |
120 |
| Istituzione: |
Università degli Studi di Napoli Federico II |
| Dipartimento: |
dep14 |
| Dottorato: |
phd054 |
| Ciclo di dottorato: |
30 |
| Coordinatore del Corso di dottorato: |
| nome | email |
|---|
| Avvedimento, Vittorio Enrico | vittorioenrico.avvedimento@unina.it |
|
| Tutor: |
| nome | email |
|---|
| Catania, Maria Rosaria | [non definito] |
|
| Data: |
11 Dicembre 2017 |
| Numero di pagine: |
120 |
| Parole chiave: |
Biofilm; Bacteria; antibiotic resistance; Alternative drugs. |
| Settori scientifico-disciplinari del MIUR: |
Area 05 - Scienze biologiche > BIO/19 - Microbiologia generale |
[error in script]
[error in script]
| Depositato il: |
27 Dic 2017 17:24 |
| Ultima modifica: |
20 Mar 2019 12:05 |
| URI: |
http://www.fedoa.unina.it/id/eprint/12172 |
Abstract
Antibiotics resistant bacteria have become over the last few decades one of the greatest threats to global health. Infections caused by multi-drug-resistant pathogens are generally difficult to treat and are often fatal. Biofilm formation has been recognized as one of the most important, and most difficult to treat, among the mechanisms conferring antibiotics tolerance to pathogens. There is currently an urgent need for novel and effective approaches to fight the global health challenge of antibiotic resistance and in particular biofilm based tolerance. In this context, antimicrobial peptides (AMP) and antimicrobial plant extracts are among the most promising solutions.
This thesis work was aimed at the discovery, characterization and evaluation of the antimicrobial, and especially anti-biofilm, activity of novel AMPs and novel plant extracts. A set of analyses integrating bioinformatics, synthetic biology and biochemical approaches has been employed to identify new antimicrobial compounds. Clinical phenotype as well as reference fungal and bacterial strains were used to test the antimicrobial and anti-biofilm potential of these new compounds. Antimicrobial activity assays were performed by microdilution method and time kill assays, while anti-biofilm activity was evaluated with biomass quantification, biofilm vitality assessment and by means of confocal laser scanner microscopy. Finally, cytotoxic experiments were performed against human cells to determine if the discovered compounds could be considered promising candidates for the development of topical antimicrobial agents.
As a first step, a cryptic AMP-like peptide named VLL-28, identified in the sequence of an archaeal protein was analyzed and characterized with efficient antifungal and anti-biofilm activities against all tested clinical strains.
Then, a second cryptic AMP-like peptide (PAP-A3), derived by in silico screening of human proteins, was identified in the Pepsinogen A activation peptide along with two other fragments (IMY25 and FLK22). These three peptides exhibited considerable antimicrobial and anti-biofilm properties against a range of pathogenic bacteria, including foodborne organisms infecting the stomach and biofilm producing strains.
Furan-motifs and lignan-motifs were than employed to identify new molecules exhibiting antimicrobial properties. This activity led to the characterization of fourteen synthetic arylfurans and lignan-like arylbenzylfurans, that in turn were tested against Gram-negative (Pseudomonas aeruginosa, Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus and S. epidermidis). One of these compounds, methyl 4-(2-hydroxybenzyl)-2-phenylfuran-3-carboxylate, was found to be active against S. aureus and S. epidermidis. This latter showed also a good anti-biofilm activity and was found to be nontoxic in human cells.
Finally, Abietic acid, a tricyclic diterpenoid derived from the resin of pine trees, was tested against Staphylococcus pseudintermedius strains and was found to be able to increase the susceptibility to Methicillin in Methicillin-resistant isolates of S. pseudintermedius (MRSP) by modulating the expression of mec genes. Moreover, Abietic acid also displayed a good anti-biofilm activity by killing almost all cells embedded in biofilm already at very low concentrations.
In conclusion, new possible sources were explored in this work to find novel antimicrobial compounds to fight the emerging antimicrobial resistance to conventional drugs. As a result, a series of new and effective antimicrobial agents were detected, characterized and tested against a wide range of pathogens.
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