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Dr. Bruno Casciaro
Center for Life Nano [email protected], Istituto Italiano di Tecnologia, Via Regina Elena 291, 00161 Rome, Italy

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0 antimicrobials
0 Biochemical and biological characterization
0 Natural Bioactive Products
0 antimicrobial peptides (AMPs)
0 Microbiology Immunology

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antimicrobial peptides (AMPs)
antimicrobials

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Journal article
Published: 21 May 2021 in Proceedings of the National Academy of Sciences
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The activity of many antibiotics depends on the initial density of cells used in bacterial growth inhibition assays. This phenomenon, termed the inoculum effect, can have important consequences for the therapeutic efficacy of the drugs, because bacterial loads vary by several orders of magnitude in clinically relevant infections. Antimicrobial peptides are a promising class of molecules in the fight against drug-resistant bacteria because they act mainly by perturbing the cell membranes rather than by inhibiting intracellular targets. Here, we report a systematic characterization of the inoculum effect for this class of antibacterial compounds. Minimum inhibitory concentration values were measured for 13 peptides (including all-D enantiomers) and peptidomimetics, covering more than seven orders of magnitude in inoculated cell density. In most cases, the inoculum effect was significant for cell densities above the standard inoculum of 5 × 105 cells/mL, while for lower densities the active concentrations remained essentially constant, with values in the micromolar range. In the case of membrane-active peptides, these data can be rationalized by considering a simple model, taking into account peptide–cell association, and hypothesizing that a threshold number of cell-bound peptide molecules is required in order to cause bacterial killing. The observed effect questions the clinical utility of activity and selectivity determinations performed at a fixed, standardized cell density. A routine evaluation of the dependence of the activity of antimicrobial peptides and peptidomimetics on the inoculum should be considered.

ACS Style

Maria Rosa Loffredo; Filippo Savini; Sara Bobone; Bruno Casciaro; Henrik Franzyk; Maria Luisa Mangoni; Lorenzo Stella. Inoculum effect of antimicrobial peptides. Proceedings of the National Academy of Sciences 2021, 118, 1 .

AMA Style

Maria Rosa Loffredo, Filippo Savini, Sara Bobone, Bruno Casciaro, Henrik Franzyk, Maria Luisa Mangoni, Lorenzo Stella. Inoculum effect of antimicrobial peptides. Proceedings of the National Academy of Sciences. 2021; 118 (21):1.

Chicago/Turabian Style

Maria Rosa Loffredo; Filippo Savini; Sara Bobone; Bruno Casciaro; Henrik Franzyk; Maria Luisa Mangoni; Lorenzo Stella. 2021. "Inoculum effect of antimicrobial peptides." Proceedings of the National Academy of Sciences 118, no. 21: 1.

Journal article
Published: 08 January 2021 in International Journal of Molecular Sciences
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Persistent infections, such as those provoked by the Gram-negative bacterium Pseudomonas aeruginosa in the lungs of cystic fibrosis (CF) patients, can induce inflammation with lung tissue damage and progressive alteration of respiratory function. Therefore, compounds having both antimicrobial and immunomodulatory activities are certainly of great advantage in fighting infectious diseases and chronic inflammation. We recently demonstrated the potent antipseudomonal efficacy of the antimicrobial peptide (AMP) Esc(1-21) and its diastereomer Esc(1-21)-1c, namely Esc peptides. Here, we confirmed this antimicrobial activity by reporting on the peptides’ ability to kill P. aeruginosa once internalized into alveolar epithelial cells. Furthermore, by means of enzyme-linked immunosorbent assay and Western blot analyses, we investigated the peptides’ ability to detoxify the bacterial lipopolysaccharide (LPS) by studying their effects on the secretion of the pro-inflammatory cytokine IL-6 as well as on the expression of cyclooxygenase-2 from macrophages activated by P. aeruginosa LPS. In addition, by a modified scratch assay we showed that both AMPs are able to stimulate the closure of a gap produced in alveolar epithelial cells when cell migration is inhibited by concentrations of Pseudomonas LPS that mimic lung infection conditions, suggesting a peptide-induced airway wound repair. Overall, these results have highlighted the two Esc peptides as valuable candidates for the development of new multifunctional therapeutics for treatment of chronic infectious disease and inflammation, as found in CF patients.

ACS Style

Floriana Cappiello; Veronica Carnicelli; Bruno Casciaro; Maria Luisa Mangoni. Antipseudomonal and Immunomodulatory Properties of Esc Peptides: Promising Features for Treatment of Chronic Infectious Diseases and Inflammation. International Journal of Molecular Sciences 2021, 22, 557 .

AMA Style

Floriana Cappiello, Veronica Carnicelli, Bruno Casciaro, Maria Luisa Mangoni. Antipseudomonal and Immunomodulatory Properties of Esc Peptides: Promising Features for Treatment of Chronic Infectious Diseases and Inflammation. International Journal of Molecular Sciences. 2021; 22 (2):557.

Chicago/Turabian Style

Floriana Cappiello; Veronica Carnicelli; Bruno Casciaro; Maria Luisa Mangoni. 2021. "Antipseudomonal and Immunomodulatory Properties of Esc Peptides: Promising Features for Treatment of Chronic Infectious Diseases and Inflammation." International Journal of Molecular Sciences 22, no. 2: 557.

Journal article
Published: 10 December 2020 in International Journal of Molecular Sciences
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Bacterial biofilms are a serious threat for human health, and the Gram-positive bacterium Staphylococcus aureus is one of the microorganisms that can easily switch from a planktonic to a sessile lifestyle, providing protection from a large variety of adverse environmental conditions. Dormant non-dividing cells with low metabolic activity, named persisters, are tolerant to antibiotic treatment and are the principal cause of recalcitrant and resistant infections, including skin infections. Antimicrobial peptides (AMPs) hold promise as new anti-infective agents to treat such infections. Here for the first time, we investigated the activity of the frog-skin AMP temporin G (TG) against preformed S. aureus biofilm including persisters, as well as its efficacy in combination with tobramycin, in inhibiting S. aureus growth. TG was found to provoke ~50 to 100% reduction of biofilm viability in the concentration range from 12.5 to 100 µM vs ATCC and clinical isolates and to be active against persister cells (about 70–80% killing at 50–100 µM). Notably, sub-inhibitory concentrations of TG in combination with tobramycin were able to significantly reduce S. aureus growth, potentiating the antibiotic power. No critical cytotoxicity was detected when TG was tested in vitro up to 100 µM against human keratinocytes, confirming its safety profile for the development of a new potential anti-infective drug, especially for treatment of bacterial skin infections.

ACS Style

Bruno Casciaro; Maria Rosa Loffredo; Floriana Cappiello; Guendalina Fabiano; Luisa Torrini; Maria Luisa Mangoni. The Antimicrobial Peptide Temporin G: Anti-Biofilm, Anti-Persister Activities, and Potentiator Effect of Tobramycin Efficacy against Staphylococcus aureus. International Journal of Molecular Sciences 2020, 21, 9410 .

AMA Style

Bruno Casciaro, Maria Rosa Loffredo, Floriana Cappiello, Guendalina Fabiano, Luisa Torrini, Maria Luisa Mangoni. The Antimicrobial Peptide Temporin G: Anti-Biofilm, Anti-Persister Activities, and Potentiator Effect of Tobramycin Efficacy against Staphylococcus aureus. International Journal of Molecular Sciences. 2020; 21 (24):9410.

Chicago/Turabian Style

Bruno Casciaro; Maria Rosa Loffredo; Floriana Cappiello; Guendalina Fabiano; Luisa Torrini; Maria Luisa Mangoni. 2020. "The Antimicrobial Peptide Temporin G: Anti-Biofilm, Anti-Persister Activities, and Potentiator Effect of Tobramycin Efficacy against Staphylococcus aureus." International Journal of Molecular Sciences 21, no. 24: 9410.

Editorial
Published: 04 November 2020 in Antibiotics
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Since the discovery of magainins from the skin secretions of the African toad Xenopus laevis by Michael Zasloff in 1987, an increasing number of antimicrobial peptides (AMPs) has been identified in different anuran species and studied in detail

ACS Style

Maria Luisa Mangoni; Bruno Casciaro. Development of Antimicrobial Peptides from Amphibians. Antibiotics 2020, 9, 772 .

AMA Style

Maria Luisa Mangoni, Bruno Casciaro. Development of Antimicrobial Peptides from Amphibians. Antibiotics. 2020; 9 (11):772.

Chicago/Turabian Style

Maria Luisa Mangoni; Bruno Casciaro. 2020. "Development of Antimicrobial Peptides from Amphibians." Antibiotics 9, no. 11: 772.

Preprint content
Published: 21 August 2020
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The activity of many antibiotics depends on the initial density of cells used in bacteria growth inhibition assays. This phenomenon, termed the inoculum effect, can have important consequences for the therapeutic efficacy of the drugs, since bacterial loads vary by several orders of magnitude in clinically relevant infections. Antimicrobial peptides are a promising class of molecules to fight drug-resistant bacteria, since they act mainly by perturbing the cell membranes rather than by inhibiting intracellular targets. Here we report the first systematic characterization of the inoculum effect for this class of antibacterial compounds. Thirteen peptides (including all-D enantiomers) and peptidomimetics were analyzed by measuring minimum inhibitory concentration values, covering more than 7 orders of magnitude in inoculated cell density. In all cases, we observed a significant inoculum effect for cell densities above 5 x 104 cells/mL, while the active concentrations remained constant (within the micromolar range) for lower densities. In the case of membrane-active peptides, these data can be rationalized by considering a simple model, taking into account peptide-cell association and hypothesizing that a threshold number of cell-bound peptide molecules is required in order to cause a killing effect. The observed effects question the clinical utility of activity and selectivity determinations performed at a fixed, standardized cell density. A routine evaluation of the inoculum dependence of the activity of antimicrobial peptides and peptidomimetics should be considered.

ACS Style

Maria Rosa Loffredo; Filippo Savini; Sara Bobone; Bruno Casciaro; Henrik Franzyk; Maria Luisa Mangoni; Lorenzo Stella. Inoculum effect of antimicrobial peptides. 2020, 1 .

AMA Style

Maria Rosa Loffredo, Filippo Savini, Sara Bobone, Bruno Casciaro, Henrik Franzyk, Maria Luisa Mangoni, Lorenzo Stella. Inoculum effect of antimicrobial peptides. . 2020; ():1.

Chicago/Turabian Style

Maria Rosa Loffredo; Filippo Savini; Sara Bobone; Bruno Casciaro; Henrik Franzyk; Maria Luisa Mangoni; Lorenzo Stella. 2020. "Inoculum effect of antimicrobial peptides." , no. : 1.

Review
Published: 09 August 2020 in Molecules
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Antibiotic resistance is now considered a worldwide problem that puts public health at risk. The onset of bacterial strains resistant to conventional antibiotics and the scarcity of new drugs have prompted scientific research to re-evaluate natural products as molecules with high biological and chemical potential. A class of natural compounds of significant importance is represented by alkaloids derived from higher plants. In this review, we have collected data obtained from various research groups on the antimicrobial activities of these alkaloids against conventional antibiotic-resistant strains. In addition, the structure–function relationship was described and commented on, highlighting the high potential of alkaloids as antimicrobials.

ACS Style

Bruno Casciaro; Laura Mangiardi; Floriana Cappiello; Isabella Romeo; Maria Rosa Loffredo; Antonia Iazzetti; Andrea Calcaterra; Antonella Goggiamani; Francesca Ghirga; Maria Luisa Mangoni; Bruno Botta; Deborah Quaglio. Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections. Molecules 2020, 25, 3619 .

AMA Style

Bruno Casciaro, Laura Mangiardi, Floriana Cappiello, Isabella Romeo, Maria Rosa Loffredo, Antonia Iazzetti, Andrea Calcaterra, Antonella Goggiamani, Francesca Ghirga, Maria Luisa Mangoni, Bruno Botta, Deborah Quaglio. Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections. Molecules. 2020; 25 (16):3619.

Chicago/Turabian Style

Bruno Casciaro; Laura Mangiardi; Floriana Cappiello; Isabella Romeo; Maria Rosa Loffredo; Antonia Iazzetti; Andrea Calcaterra; Antonella Goggiamani; Francesca Ghirga; Maria Luisa Mangoni; Bruno Botta; Deborah Quaglio. 2020. "Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections." Molecules 25, no. 16: 3619.

Research article
Published: 27 July 2020 in The Journal of Organic Chemistry
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Colistin is a last-resort antibiotic for treatment of multidrug resistant Gram-negative bacterial infections. Recently, a natural ent-beyerene diterpene was identified as a promising inhibitor of the enzyme responsible for colistin re-sistance mediated by lipid A aminoarabinosylation, in Gram-negative bacteria, namely ArnT (undecaprenyl phospha-te-alpha-4-amino-4-deoxy-L-arabinose arabinosyl transferase). Here, semi-synthetic analogs of hit were designed, synthetized and tested against colistin-resistant Pseudomonas aeruginosa strains including clinical isolates, to exploit the versatility of the diterpene scaffold. Microbiological assays coupled with molecular modeling indicated that for a more efficient colistin adjuvant activity, likely resulting from inhibition of the ArnT activity by the selected com-pounds and therefore from their interaction with the catalytic site of ArnT, an ent-beyerane scaffold is required along with an oxalate like group at C-18/C-19, or a sugar residue at C-19 to resemble L-Ara4N. The ent-beyerane skeleton is identified for the first time as a privileged scaffold for further cost-effective development of valuable colistin re-sistance inhibitors.

ACS Style

Deborah Quaglio; Maria Luisa Mangoni; Roberta Stefanelli; Silvia Corradi; Bruno Casciaro; Valeria Vergine; Federica Lucantoni; Luca Cavinato; Silvia Cammarone; Maria Rosa Loffredo; Floriana Cappiello; Andrea Calcaterra; Silvia Erazo; Francesca Ghirga; Mattia Mori; Francesco Imperi; Fiorentina Ascenzioni; Bruno Botta. ent-Beyerane Diterpenes as a Key Platform for the Development of ArnT-Mediated Colistin Resistance Inhibitors. The Journal of Organic Chemistry 2020, 85, 10891 -10901.

AMA Style

Deborah Quaglio, Maria Luisa Mangoni, Roberta Stefanelli, Silvia Corradi, Bruno Casciaro, Valeria Vergine, Federica Lucantoni, Luca Cavinato, Silvia Cammarone, Maria Rosa Loffredo, Floriana Cappiello, Andrea Calcaterra, Silvia Erazo, Francesca Ghirga, Mattia Mori, Francesco Imperi, Fiorentina Ascenzioni, Bruno Botta. ent-Beyerane Diterpenes as a Key Platform for the Development of ArnT-Mediated Colistin Resistance Inhibitors. The Journal of Organic Chemistry. 2020; 85 (16):10891-10901.

Chicago/Turabian Style

Deborah Quaglio; Maria Luisa Mangoni; Roberta Stefanelli; Silvia Corradi; Bruno Casciaro; Valeria Vergine; Federica Lucantoni; Luca Cavinato; Silvia Cammarone; Maria Rosa Loffredo; Floriana Cappiello; Andrea Calcaterra; Silvia Erazo; Francesca Ghirga; Mattia Mori; Francesco Imperi; Fiorentina Ascenzioni; Bruno Botta. 2020. "ent-Beyerane Diterpenes as a Key Platform for the Development of ArnT-Mediated Colistin Resistance Inhibitors." The Journal of Organic Chemistry 85, no. 16: 10891-10901.

Journal article
Published: 26 July 2020 in Antibiotics
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Corynebacterium jeikeium is a commensal bacterium that colonizes human skin, and it is part of the normal bacterial flora. In non-risk subjects, it can be the cause of bad body smell due to the generation of volatile odorous metabolites, especially in the wet parts of the body that this bacterium often colonizes (i.e., groin and axillary regions). Importantly, in the last few decades, there have been increasing cases of serious infections provoked by this bacterium, especially in immunocompromised or hospitalized patients who have undergone installation of prostheses or catheters. The ease in developing resistance to commonly-used antibiotics (i.e., glycopeptides) has made the search for new antimicrobial compounds of clinical importance. Here, for the first time, we characterize the antimicrobial activity of some selected frog skin-derived antimicrobial peptides (AMPs) against C. jeikeium by determining their minimum inhibitory and bactericidal concentrations (MIC and MBC) by a microdilution method. The results highlight esculentin-1b(1-18) [Esc(1-18)] and esculentin-1a(1-21) [Esc(1-21)] as the most active AMPs with MIC and MBC of 4–8 and 0.125–0.25 µM, respectively, along with a non-toxic profile after a short- and long-term (40 min and 24 h) treatment of mammalian cells. Overall, these findings indicate the high potentiality of Esc(1-18) and Esc(1-21) as (i) alternative antimicrobials against C. jeikeium infections and/or as (ii) additives in cosmetic products (creams, deodorants) to reduce the production of bad body odor.

ACS Style

Bruno Casciaro; Maria Rosa Loffredo; Floriana Cappiello; Walter Verrusio; Vito Domenico Corleto; Maria Luisa Mangoni. Frog Skin-Derived Peptides Against Corynebacterium jeikeium: Correlation between Antibacterial and Cytotoxic Activities. Antibiotics 2020, 9, 448 .

AMA Style

Bruno Casciaro, Maria Rosa Loffredo, Floriana Cappiello, Walter Verrusio, Vito Domenico Corleto, Maria Luisa Mangoni. Frog Skin-Derived Peptides Against Corynebacterium jeikeium: Correlation between Antibacterial and Cytotoxic Activities. Antibiotics. 2020; 9 (8):448.

Chicago/Turabian Style

Bruno Casciaro; Maria Rosa Loffredo; Floriana Cappiello; Walter Verrusio; Vito Domenico Corleto; Maria Luisa Mangoni. 2020. "Frog Skin-Derived Peptides Against Corynebacterium jeikeium: Correlation between Antibacterial and Cytotoxic Activities." Antibiotics 9, no. 8: 448.

Review
Published: 13 June 2020 in Antibiotics
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The discovery of antibiotics has revolutionized the medicine and treatment of microbial infections. However, the current scenario has highlighted the difficulties in marketing new antibiotics and an exponential increase in the appearance of resistant strains. On the other hand, research in the field of drug-discovery has revaluated the potential of natural products as a unique source for new biologically active molecules and scaffolds for the medicinal chemistry. In this review, we first contextualized the worldwide problem of antibiotic resistance and the importance that natural products of plant origin acquire as a source of new lead compounds. We then focused on terpenes and their potential development as antimicrobials, highlighting those studies that showed an activity against conventional antibiotic-resistant strains.

ACS Style

Floriana Cappiello; Maria Rosa Loffredo; Cristina Del Plato; Silvia Cammarone; Bruno Casciaro; Deborah Quaglio; Maria Luisa Mangoni; Bruno Botta; Francesca Ghirga. The Revaluation of Plant-Derived Terpenes to Fight Antibiotic-Resistant Infections. Antibiotics 2020, 9, 1 .

AMA Style

Floriana Cappiello, Maria Rosa Loffredo, Cristina Del Plato, Silvia Cammarone, Bruno Casciaro, Deborah Quaglio, Maria Luisa Mangoni, Bruno Botta, Francesca Ghirga. The Revaluation of Plant-Derived Terpenes to Fight Antibiotic-Resistant Infections. Antibiotics. 2020; 9 (6):1.

Chicago/Turabian Style

Floriana Cappiello; Maria Rosa Loffredo; Cristina Del Plato; Silvia Cammarone; Bruno Casciaro; Deborah Quaglio; Maria Luisa Mangoni; Bruno Botta; Francesca Ghirga. 2020. "The Revaluation of Plant-Derived Terpenes to Fight Antibiotic-Resistant Infections." Antibiotics 9, no. 6: 1.

Journal article
Published: 11 June 2020 in Current Topics in Medicinal Chemistry
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The frequent occurrence of multidrug-resistant strains to conventional antimicrobials has led to a clear decline in antibiotic therapies. Therefore, new molecules with different mechanisms of action are extremely necessary. Due to their unique properties, antimicrobial peptides (AMPs) represent a valid alternative to conventional antibiotics and many of them have been characterized for their activity and cytotoxicity. However, the effects that these peptides cause at concentrations below the minimum growth inhibitory concentration (MIC) have yet to be fully analyzed along with the underlying molecular mechanism. In this mini-review, the ability of AMPs to synergize with different antibiotic classes or different natural compounds is examined. Furthermore, data on microbial resistance induction are reported to highlight the importance of antibiotic resistance in the fight against infections. Finally, the effects that sub-MIC levels of AMPs can have on the bacterial pathogenicity are summarized while showing how signaling pathways can be valid therapeutic targets for the treatment of infectious diseases. All these aspects support the high potential of AMPs as lead compounds for the development of new drugs with antibacterial and immunomodulatory activities.

ACS Style

Bruno Casciaro; Floriana Cappiello; Walter Verrusio; Mauro Cacciafesta; Maria Luisa Mangoni. Antimicrobial Peptides and their Multiple Effects at Sub-Inhibitory Concentrations. Current Topics in Medicinal Chemistry 2020, 20, 1264 -1273.

AMA Style

Bruno Casciaro, Floriana Cappiello, Walter Verrusio, Mauro Cacciafesta, Maria Luisa Mangoni. Antimicrobial Peptides and their Multiple Effects at Sub-Inhibitory Concentrations. Current Topics in Medicinal Chemistry. 2020; 20 (14):1264-1273.

Chicago/Turabian Style

Bruno Casciaro; Floriana Cappiello; Walter Verrusio; Mauro Cacciafesta; Maria Luisa Mangoni. 2020. "Antimicrobial Peptides and their Multiple Effects at Sub-Inhibitory Concentrations." Current Topics in Medicinal Chemistry 20, no. 14: 1264-1273.

Journal article
Published: 08 June 2020 in Journal of Antimicrobial Chemotherapy
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Background Colistin is a last-resort treatment option for many MDR Gram-negative bacteria. The covalent addition of l-aminoarabinose to the lipid A moiety of LPS is the main colistin resistance mechanism in the human pathogen Pseudomonas aeruginosa. Objectives Identification (by in silico screening of a chemical library) of potential inhibitors of ArnT, which catalyses the last committed step of lipid A aminoarabinosylation, and their validation in vitro as colistin adjuvants. Methods The available ArnT crystal structure was used for a docking-based virtual screening of an in-house library of natural products. The resulting putative ArnT inhibitors were tested in growth inhibition assays using a reference colistin-resistant P. aeruginosa strain. The most promising compound was further characterized for its range of activity, specificity and cytotoxicity. Additionally, the effect of the compound on lipid A aminoarabinosylation was verified by MS analyses of lipid A. Results A putative ArnT inhibitor (BBN149) was discovered by molecular docking and demonstrated to specifically potentiate colistin activity in colistin-resistant P. aeruginosa isolates, without relevant effect on colistin-susceptible strains. BBN149 also showed adjuvant activity against colistin-resistant Klebsiella pneumoniae and low toxicity to bronchial epithelial cells. Lipid A aminoarabinosylation was reduced in BBN149-treated cells, although only partially. Conclusions This study demonstrates that in silico screening targeting ArnT can successfully identify inhibitors of colistin resistance and provides a promising lead compound for the development of colistin adjuvants for the treatment of MDR bacterial infections.

ACS Style

Francesca Ghirga; Roberta Stefanelli; Luca Cavinato; Alessandra Lo Sciuto; Silvia Corradi; Deborah Quaglio; Andrea Calcaterra; Bruno Casciaro; Maria Rosa Loffredo; Floriana Cappiello; Patrizia Morelli; Alberto Antonelli; Gian Maria Rossolini; Marialuisa Mangoni; Carmine Mancone; Bruno Botta; Mattia Mori; Fiorentina Ascenzioni; Francesco Imperi. A novel colistin adjuvant identified by virtual screening for ArnT inhibitors. Journal of Antimicrobial Chemotherapy 2020, 75, 2564 -2572.

AMA Style

Francesca Ghirga, Roberta Stefanelli, Luca Cavinato, Alessandra Lo Sciuto, Silvia Corradi, Deborah Quaglio, Andrea Calcaterra, Bruno Casciaro, Maria Rosa Loffredo, Floriana Cappiello, Patrizia Morelli, Alberto Antonelli, Gian Maria Rossolini, Marialuisa Mangoni, Carmine Mancone, Bruno Botta, Mattia Mori, Fiorentina Ascenzioni, Francesco Imperi. A novel colistin adjuvant identified by virtual screening for ArnT inhibitors. Journal of Antimicrobial Chemotherapy. 2020; 75 (9):2564-2572.

Chicago/Turabian Style

Francesca Ghirga; Roberta Stefanelli; Luca Cavinato; Alessandra Lo Sciuto; Silvia Corradi; Deborah Quaglio; Andrea Calcaterra; Bruno Casciaro; Maria Rosa Loffredo; Floriana Cappiello; Patrizia Morelli; Alberto Antonelli; Gian Maria Rossolini; Marialuisa Mangoni; Carmine Mancone; Bruno Botta; Mattia Mori; Fiorentina Ascenzioni; Francesco Imperi. 2020. "A novel colistin adjuvant identified by virtual screening for ArnT inhibitors." Journal of Antimicrobial Chemotherapy 75, no. 9: 2564-2572.

Journal article
Published: 29 April 2020 in Current Protein & Peptide Science
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ACS Style

Bruno Casciaro; Maria Luisa Mangoni. Nanotechnologies to Improve the Pharmacological Profile of Therapeutic Peptides. Current Protein & Peptide Science 2020, 21, 332 -333.

AMA Style

Bruno Casciaro, Maria Luisa Mangoni. Nanotechnologies to Improve the Pharmacological Profile of Therapeutic Peptides. Current Protein & Peptide Science. 2020; 21 (4):332-333.

Chicago/Turabian Style

Bruno Casciaro; Maria Luisa Mangoni. 2020. "Nanotechnologies to Improve the Pharmacological Profile of Therapeutic Peptides." Current Protein & Peptide Science 21, no. 4: 332-333.

Journal article
Published: 29 April 2020 in Current Protein & Peptide Science
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Cationic antimicrobial peptides (AMPs) are an interesting class of gene-encoded molecules endowed with a broad-spectrum of anti-infective activity and immunomodulatory properties. They represent promising candidates for the development of new antibiotics, mainly due to their membraneperturbing mechanism of action that very rarely induces microbial resistance. However, bringing AMPs into the clinical field is hampered by some intrinsic limitations, encompassing low peptide bioavailability at the target site and high peptide susceptibility to proteolytic degradation. In this regard, nanotechnologies represent an innovative strategy to circumvent these issues. According to the literature, a large variety of nanoparticulate systems have been employed for drug-delivery, bioimaging, biosensors or nanoantibiotics. The possibility of conjugating different types of molecules, including AMPs, to these systems, allows the production of nanoformulations able to enhance the biological profile of the compound while reducing its cytotoxicity and prolonging its residence time. In this minireview, inorganic gold nanoparticles (NPs) and biodegradable polymeric NPs made of poly(lactide-coglycolide) are described with particular emphasis on examples of the conjugation of AMPs to them, to highlight the great potential of such nanoformulations as alternative antimicrobials.

ACS Style

Bruno Casciaro; Francesca Ghirga; Deborah Quaglio; Maria Luisa Mangoni. Inorganic Gold and Polymeric Poly(Lactide-co-glycolide) Nanoparticles as Novel Strategies to Ameliorate the Biological Properties of Antimicrobial Peptides. Current Protein & Peptide Science 2020, 21, 429 -438.

AMA Style

Bruno Casciaro, Francesca Ghirga, Deborah Quaglio, Maria Luisa Mangoni. Inorganic Gold and Polymeric Poly(Lactide-co-glycolide) Nanoparticles as Novel Strategies to Ameliorate the Biological Properties of Antimicrobial Peptides. Current Protein & Peptide Science. 2020; 21 (4):429-438.

Chicago/Turabian Style

Bruno Casciaro; Francesca Ghirga; Deborah Quaglio; Maria Luisa Mangoni. 2020. "Inorganic Gold and Polymeric Poly(Lactide-co-glycolide) Nanoparticles as Novel Strategies to Ameliorate the Biological Properties of Antimicrobial Peptides." Current Protein & Peptide Science 21, no. 4: 429-438.

Journal article
Published: 27 March 2020 in Current Medicinal Chemistry
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Antimicrobial Peptides (AMPs) are the key effectors of the innate immunity and represent promising molecules for the development of new antibacterial drugs. However, to achieve this goal, some problems need to be overcome: (i) the cytotoxic effects at high concentrations; (ii) the poor biostability and (iii) the difficulty in reaching the target site. Frog skin is one of the richest natural storehouses of AMPs, and over the years, many peptides have been isolated from it, characterized and classified into several families encompassing temporins, brevinins, nigrocins and esculentins. In this review, we summarized how the isolation/characterization of peptides belonging to the esculentin-1 family drove us to the design of an analogue, i.e. esculentin-1a(1-21)NH2, with a powerful antimicrobial action and immunomodulatory properties. The peptide had a wide spectrum of activity, especially against the opportunistic Gram-negative bacterium Pseudomonas aeruginosa. We described the structural features and the in vitro/in vivo biological characterization of this peptide as well as the strategies used to improve its biological properties. Among them: (i) the design of a diastereomer carrying Damino acids in order to reduce the peptide’s cytotoxicity and improve its half-life; (ii) the covalent conjugation of the peptide to gold nanoparticles or its encapsulation into poly(lactide- co-glycolide) nanoparticles; and (iii) the peptide immobilization to biomedical devices (such as silicon hydrogel contact lenses) to obtain an antibacterial surface able to reduce microbial growth and attachment. Summing up the best results obtained so far, this review traces all the steps that led these frog-skin AMPs to the direction of peptide-based drugs for clinical use.

ACS Style

Bruno Casciaro; Floriana Cappiello; Maria Rosa Loffredo; Francesca Ghirga; Maria Luisa Mangoni. The Potential of Frog Skin Peptides for Anti-Infective Therapies: The Case of Esculentin-1a(1-21)NH2. Current Medicinal Chemistry 2020, 27, 1405 -1419.

AMA Style

Bruno Casciaro, Floriana Cappiello, Maria Rosa Loffredo, Francesca Ghirga, Maria Luisa Mangoni. The Potential of Frog Skin Peptides for Anti-Infective Therapies: The Case of Esculentin-1a(1-21)NH2. Current Medicinal Chemistry. 2020; 27 (9):1405-1419.

Chicago/Turabian Style

Bruno Casciaro; Floriana Cappiello; Maria Rosa Loffredo; Francesca Ghirga; Maria Luisa Mangoni. 2020. "The Potential of Frog Skin Peptides for Anti-Infective Therapies: The Case of Esculentin-1a(1-21)NH2." Current Medicinal Chemistry 27, no. 9: 1405-1419.

Rapid communication
Published: 30 January 2020 in ACS Medicinal Chemistry Letters
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Novel diterpenoids were isolated from the extracts of Fabiana densa var. ramulosa and found to display a selective activity against Gram-positive bacterial strains with negligible cytotoxicity toward human keratinocytes. This study highlighted the role played by the acidic group at C18 of the tetracyclic ent-beyerene scaffold for antibacterial effects and how the length and flexibility of the alkyl chain between the two carbonyl groups are crucial factors to increase the antimicrobial activity of the molecules, supporting the development of natural products from F. densa and their derivatives for treatment of microbial infections.

ACS Style

Deborah Quaglio; Silvia Corradi; Silvia Erazo; Valeria Vergine; Simone Berardozzi; Fabio Sciubba; Floriana Cappiello; Maria Elisa Crestoni; Fiorentina Ascenzioni; Francesco Imperi; Franco Delle Monache; Mattia Mori; Maria Rosa Loffredo; Francesca Ghirga; Bruno Casciaro; Bruno Botta; Maria Luisa Mangoni. Structural Elucidation and Antimicrobial Characterization of Novel Diterpenoids from Fabiana densa var. ramulosa. ACS Medicinal Chemistry Letters 2020, 11, 760 -765.

AMA Style

Deborah Quaglio, Silvia Corradi, Silvia Erazo, Valeria Vergine, Simone Berardozzi, Fabio Sciubba, Floriana Cappiello, Maria Elisa Crestoni, Fiorentina Ascenzioni, Francesco Imperi, Franco Delle Monache, Mattia Mori, Maria Rosa Loffredo, Francesca Ghirga, Bruno Casciaro, Bruno Botta, Maria Luisa Mangoni. Structural Elucidation and Antimicrobial Characterization of Novel Diterpenoids from Fabiana densa var. ramulosa. ACS Medicinal Chemistry Letters. 2020; 11 (5):760-765.

Chicago/Turabian Style

Deborah Quaglio; Silvia Corradi; Silvia Erazo; Valeria Vergine; Simone Berardozzi; Fabio Sciubba; Floriana Cappiello; Maria Elisa Crestoni; Fiorentina Ascenzioni; Francesco Imperi; Franco Delle Monache; Mattia Mori; Maria Rosa Loffredo; Francesca Ghirga; Bruno Casciaro; Bruno Botta; Maria Luisa Mangoni. 2020. "Structural Elucidation and Antimicrobial Characterization of Novel Diterpenoids from Fabiana densa var. ramulosa." ACS Medicinal Chemistry Letters 11, no. 5: 760-765.

Protocol
Published: 28 January 2020 in Immunity in Insects
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Antimicrobial peptides (AMPs) represent an interesting class of molecules with expanding properties. Nature is the primary source of AMPs since they are produced by most living organisms including prokaryotes, plants, and animals. Thanks to their hundreds of thousands of species on earth, insects are one of the most abundant and varied resources of AMPs. Among these, many families have already been well characterized while new AMPs are continuously discovered. In this chapter, the main methods for the in vitro evaluation of the biological properties of AMPs are described. In particular, to examine the antimicrobial activity, the inhibition zone assay and the techniques for the determination of the minimal inhibitory concentration and the bactericidal concentration are reported in detail. For the evaluation of the possible cytotoxic effect toward mammalian cells, the hemolytic test and the colorimetric assay based on the reduction of 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide are also described.

ACS Style

Bruno Casciaro; Floriana Cappiello; Maria Rosa Loffredo; Maria Luisa Mangoni. Methods for the In Vitro Examination of the Antibacterial and Cytotoxic Activities of Antimicrobial Peptides. Immunity in Insects 2020, 147 -162.

AMA Style

Bruno Casciaro, Floriana Cappiello, Maria Rosa Loffredo, Maria Luisa Mangoni. Methods for the In Vitro Examination of the Antibacterial and Cytotoxic Activities of Antimicrobial Peptides. Immunity in Insects. 2020; ():147-162.

Chicago/Turabian Style

Bruno Casciaro; Floriana Cappiello; Maria Rosa Loffredo; Maria Luisa Mangoni. 2020. "Methods for the In Vitro Examination of the Antibacterial and Cytotoxic Activities of Antimicrobial Peptides." Immunity in Insects , no. : 147-162.

Research paper
Published: 01 January 2020 in Journal of Enzyme Inhibition and Medicinal Chemistry
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The rapid development of antimicrobial resistance is pushing the search in the discovering of novel antimicrobial molecules to prevent and treat bacterial infections. Self-assembling antimicrobial peptides, as the lipidated peptides, are a novel and promising class of molecules capable of meeting this need. Based on previous work on Temporin L analogs, several new molecules lipidated at the N- or and the C-terminus were synthesised. Our goal is to improve membrane interactions through finely tuning self-assembly to reduce oligomerisation in aqueous solution and enhance self-assembly in bacterial membranes while reducing toxicity against human cells. The results here reported show that the length of the aliphatic moiety is a key factor to control target cell specificity and the oligomeric state of peptides either in aqueous solution or in a membrane-mimicking environment. The results of this study pave the way for the design of novel molecules with enhanced activities.

ACS Style

Rosa Bellavita; Annarita Falanga; Elisabetta Buommino; Francesco Merlino; Bruno Casciaro; Floriana Cappiello; Maria Luisa Mangoni; Ettore Novellino; Maria Rosaria Catania; Rossella Paolillo; Paolo Grieco; Stefania Galdieroa. Novel temporin L antimicrobial peptides: promoting self-assembling by lipidic tags to tackle superbugs. Journal of Enzyme Inhibition and Medicinal Chemistry 2020, 35, 1751 -1764.

AMA Style

Rosa Bellavita, Annarita Falanga, Elisabetta Buommino, Francesco Merlino, Bruno Casciaro, Floriana Cappiello, Maria Luisa Mangoni, Ettore Novellino, Maria Rosaria Catania, Rossella Paolillo, Paolo Grieco, Stefania Galdieroa. Novel temporin L antimicrobial peptides: promoting self-assembling by lipidic tags to tackle superbugs. Journal of Enzyme Inhibition and Medicinal Chemistry. 2020; 35 (1):1751-1764.

Chicago/Turabian Style

Rosa Bellavita; Annarita Falanga; Elisabetta Buommino; Francesco Merlino; Bruno Casciaro; Floriana Cappiello; Maria Luisa Mangoni; Ettore Novellino; Maria Rosaria Catania; Rossella Paolillo; Paolo Grieco; Stefania Galdieroa. 2020. "Novel temporin L antimicrobial peptides: promoting self-assembling by lipidic tags to tackle superbugs." Journal of Enzyme Inhibition and Medicinal Chemistry 35, no. 1: 1751-1764.

Journal article
Published: 12 December 2019 in Scientific Reports
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The airway epithelium is seriously damaged upon pulmonary Pseudomonas aeruginosa infection, especially in cystic fibrosis (CF) sufferers. Therefore, the discovery of novel anti-infective agents accelerating healing of infected injured tissues is crucial. The antipseudomonal peptides esculentin-1a(1–21)NH2 and its diastereomer Esc(1–21)-1c (Esc peptides) hold promise in this respect. In fact, they stimulate airway epithelial wound repair, but no mechanistic insights are available. Here we demonstrated that this process occurs through promotion of cell migration by an indirect activation of epidermal growth factor receptor mediated by metalloproteinases. Furthermore, we showed an increased expression of metalloproteinase 9, at both gene and protein levels, in peptide-treated bronchial epithelial cells with a functional or mutated form of CF transmembrane conductance regulator. In addition, the two peptides counteracted the inhibitory effect of Pseudomonas lipopolysaccharide (mimicking an infection condition) on the wound healing activity of the airway epithelium, and they enhanced the production of interleukin-8 from both types of cells. Finally, no immunogenicity was discovered for Esc peptides, suggesting their potential safety for clinical usage. Besides representing a step forward in understanding the molecular mechanism underlying the peptide-induced wound healing activity, these studies have contributed to highlight Esc peptides as valuable therapeutics with multiple functions.

ACS Style

Floriana Cappiello; Danilo Ranieri; Veronica Carnicelli; Bruno Casciaro; Han-Tang Chen; Loretta Ferrera; Y. Peter Di; Maria Luisa Mangoni. Bronchial epithelium repair by Esculentin-1a-derived antimicrobial peptides: involvement of metalloproteinase-9 and interleukin-8, and evaluation of peptides’ immunogenicity. Scientific Reports 2019, 9, 1 -13.

AMA Style

Floriana Cappiello, Danilo Ranieri, Veronica Carnicelli, Bruno Casciaro, Han-Tang Chen, Loretta Ferrera, Y. Peter Di, Maria Luisa Mangoni. Bronchial epithelium repair by Esculentin-1a-derived antimicrobial peptides: involvement of metalloproteinase-9 and interleukin-8, and evaluation of peptides’ immunogenicity. Scientific Reports. 2019; 9 (1):1-13.

Chicago/Turabian Style

Floriana Cappiello; Danilo Ranieri; Veronica Carnicelli; Bruno Casciaro; Han-Tang Chen; Loretta Ferrera; Y. Peter Di; Maria Luisa Mangoni. 2019. "Bronchial epithelium repair by Esculentin-1a-derived antimicrobial peptides: involvement of metalloproteinase-9 and interleukin-8, and evaluation of peptides’ immunogenicity." Scientific Reports 9, no. 1: 1-13.

Journal article
Published: 01 September 2019 in Toxins
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Staphylococcus aureus is a major human pathogen causing a wide range of nosocomial infections including pulmonary, urinary, and skin infections. Notably, the emergence of bacterial strains resistant to conventional antibiotics has prompted researchers to find new compounds capable of killing these pathogens. Nature is undoubtedly an invaluable source of bioactive molecules characterized by an ample chemical diversity. They can act as unique platform providing new scaffolds for further chemical modifications in order to obtain compounds with optimized biological activity. A class of natural compounds with a variety of biological activities is represented by alkaloids, important secondary metabolites produced by a large number of organisms including bacteria, fungi, plants, and animals. In this work, starting from the screening of 39 alkaloids retrieved from a unique in-house library, we identified a heterodimer β-carboline alkaloid, nigritanine, with a potent anti-Staphylococcus action. Nigritanine, isolated from Strychnos nigritana, was characterized for its antimicrobial activity against a reference and three clinical isolates of S. aureus. Its potential cytotoxicity was also evaluated at short and long term against mammalian red blood cells and human keratinocytes, respectively. Nigritanine showed a remarkable antimicrobial activity (minimum inhibitory concentration of 128 µM) without being toxic in vitro to both tested cells. The analysis of the antibacterial activity related to the nigritanine scaffold furnished new insights in the structure–activity relationships (SARs) of β-carboline, confirming that dimerization improves its antibacterial activity. Taking into account these interesting results, nigritanine can be considered as a promising candidate for the development of new antimicrobial molecules for the treatment of S. aureus-induced infections.

ACS Style

Bruno Casciaro; Andrea Calcaterra; Floriana Cappiello; Mattia Mori; Maria Loffredo; Francesca Ghirga; Maria Mangoni; Bruno Botta; Deborah Quaglio. Nigritanine as a New Potential Antimicrobial Alkaloid for the Treatment of Staphylococcus aureus-Induced Infections. Toxins 2019, 11, 511 .

AMA Style

Bruno Casciaro, Andrea Calcaterra, Floriana Cappiello, Mattia Mori, Maria Loffredo, Francesca Ghirga, Maria Mangoni, Bruno Botta, Deborah Quaglio. Nigritanine as a New Potential Antimicrobial Alkaloid for the Treatment of Staphylococcus aureus-Induced Infections. Toxins. 2019; 11 (9):511.

Chicago/Turabian Style

Bruno Casciaro; Andrea Calcaterra; Floriana Cappiello; Mattia Mori; Maria Loffredo; Francesca Ghirga; Maria Mangoni; Bruno Botta; Deborah Quaglio. 2019. "Nigritanine as a New Potential Antimicrobial Alkaloid for the Treatment of Staphylococcus aureus-Induced Infections." Toxins 11, no. 9: 511.

Journal article
Published: 03 June 2019 in ChemMedChem
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Previously, we identified a potent antimicrobial analogue of temporin L (TL), [Pro3 ]TL, in which glutamine at position 3 was substituted with proline. In this study, a series of analogues in which position 3 is substituted with non-natural proline derivatives, was investigated for correlations between the conformational properties of the compounds and their antibacterial, cytotoxic, and hemolytic activities. Non-natural proline analogues with substituents at position 4 of the pyrrolidine ring were considered. Structure-activity relationship (SAR) studies of these analogues were performed by means of antimicrobial and cytotoxicity assays along with circular dichroism (CD) and NMR spectroscopic analyses for selected compounds. The most promising peptides were additionally evaluated for their activity against some representative veterinary microbial strains to compare with those from human strains. We identified novel analogues with interesting properties that make them attractive lead compounds.

ACS Style

Elisabetta Buommino; Alfonso Carotenuto; Ignazio Antignano; Rosa Bellavita; Bruno Casciaro; Maria Rosa Loffredo; Francesco Merlino; Ettore Novellino; Maria Luisa Mangoni; Francesca Paola Nocera; Diego Brancaccio; Pasqualina Punzi; Daniela Roversi; Raffaele Ingenito; Elisabetta Bianchi; Paolo Grieco. The Outcomes of Decorated Prolines in the Discovery of Antimicrobial Peptides from Temporin-L. ChemMedChem 2019, 14, 1283 -1290.

AMA Style

Elisabetta Buommino, Alfonso Carotenuto, Ignazio Antignano, Rosa Bellavita, Bruno Casciaro, Maria Rosa Loffredo, Francesco Merlino, Ettore Novellino, Maria Luisa Mangoni, Francesca Paola Nocera, Diego Brancaccio, Pasqualina Punzi, Daniela Roversi, Raffaele Ingenito, Elisabetta Bianchi, Paolo Grieco. The Outcomes of Decorated Prolines in the Discovery of Antimicrobial Peptides from Temporin-L. ChemMedChem. 2019; 14 (13):1283-1290.

Chicago/Turabian Style

Elisabetta Buommino; Alfonso Carotenuto; Ignazio Antignano; Rosa Bellavita; Bruno Casciaro; Maria Rosa Loffredo; Francesco Merlino; Ettore Novellino; Maria Luisa Mangoni; Francesca Paola Nocera; Diego Brancaccio; Pasqualina Punzi; Daniela Roversi; Raffaele Ingenito; Elisabetta Bianchi; Paolo Grieco. 2019. "The Outcomes of Decorated Prolines in the Discovery of Antimicrobial Peptides from Temporin-L." ChemMedChem 14, no. 13: 1283-1290.